• English
  • Korean
  • Chinese
市場調査レポート - 70916

細胞治療:技術・市場・企業

Cell Therapy - Technologies, Markets and Companies

発行 Jain Pharmabiotech
出版日 ページ情報 英文
価格
細胞治療:技術・市場・企業 Cell Therapy - Technologies, Markets and Companies
出版日: 2014年03月01日 ページ情報: 英文
概要

当レポートでは、医療活動で重要な役割を担う細胞治療技術についての最新調査データから、創薬における細胞の役割などを分析するほか、同分野の関連企業、学術機関に関する情報を提供すべく、概略下記の構成でお届けします。

パートI

エグゼクティブサマリー

第1章 細胞治療についてのイントロダクション

  • イントロダクション
  • 細胞治療の偉業史
  • 細胞治療技術の相関性
  • 細胞・組織の移植
  • 細胞とタンパク質、遺伝子治療
  • 細胞治療と再生医療
  • 細胞治療と組織工学
  • 疾患関与細胞に基く治療法
  • 細胞を治療に利用することの利点
  • 細胞利用の薬物送達

第2章 細胞治療技術

  • イントロダクション
  • 治療に使用される細胞の種類
  • 細胞の供給源
  • 細胞治療の基礎技術
  • 細胞利用の薬物送達
  • 細胞治療のための薬品送達システム
  • 人工細胞
  • 細胞のカプセル化
  • 電気穿孔法(エレクトロポレーション)
  • 遺伝子治療
  • 細胞の生体内追跡
  • 細胞治療の発展におけるナノテクノロジーの役割
  • 臓器発達への細胞移植
  • 細胞移植と公差
  • 病原性体細胞の切除と交換

第3章 幹細胞

  • イントロダクション
  • 幹細胞の生物学
  • 幹細胞の供給源
  • ヒト体細胞由来の人工多能性幹細胞(iPS細胞)
  • 条件付きで自己複製する誘発前駆細胞
  • 成人ヒト幹細胞の供給源
  • 「成人幹細胞」対「胚幹細胞(ES細胞)
  • 供給源によるヒト幹細胞の比較
  • VENT(Ventrally Emigrating Neural Tube)細胞
  • 幹細胞銀行
  • 幹細胞技術
  • 幹細胞の用途
  • 幹細胞技術が向き合う今後の課題
  • 学術機関における幹細胞研究
  • 幹細胞技術に関与する企業
  • 幹細胞についての結び
  • 幹細胞研究における今後の課題と展望

第4章 細胞治療の臨床用途

  • イントロダクション
  • 血液疾患に対する細胞治療
  • 免疫疾患に対する細胞治療
  • ウィルス性感染症に対する細胞治療
  • リソソーム蓄積症の細胞治療
  • 真性糖尿病に対する細胞治療
  • 消化器疾患の細胞治療
  • 肝臓疾患に対する細胞治療
  • 腎臓疾患の細胞治療
  • 肺疾患に対する細胞治療
  • 骨・関節疾患に対する細胞治療
  • 眼球疾患に対する細胞治療
  • 放射線症に対する幹細胞移植
  • 再生医療への細胞治療
  • 創傷治癒:皮膚・軟組織の修復
  • 組織工学および再建手術における組織工学の役割
  • 若返りに向けた細胞治療
  • スポーツにおける能力強化に向けた細胞治療
  • 獣医学における幹細胞の応用

第5章 心疾患に対する細胞治療

  • イントロダクション
  • 心筋虚血障害に対する現行療法の限界
  • 心疾患に対する細胞治療の種類
  • アテローム性冠動脈疾患に対する細胞治療
  • 心臓への細胞送達方法
  • 血管再開通術のための細胞治療
  • 心血管組織修復における細胞の役割
  • 心臓修復における幹細胞の役割
  • 遺伝子組み換え細胞の移植
  • 先天性心臓欠陥矯正のための胚性幹細胞(ESC)
  • 心臓手術のための心血管前駆細胞
  • 慢性心筋虚血に使用される自己幹細胞
  • 心血管組織工学における細胞の役割
  • 末梢血管疾患に対する細胞治療
  • 心疾患における細胞治療の役割
  • 心臓疾患細胞治療の利点のメカニズム
  • 心臓疾患細胞治療に不可欠な評価
  • 脳血管疾患細胞治療の将来的方向性

第6章 がんに対する細胞治療

  • イントロダクション
  • がんに対する細胞治療技術
  • 抗がん治療の細胞利用送達
  • がんに対する細胞免疫療法
  • がんワクチン
  • 幹細胞利用の抗がん治療
  • 細胞利用がん治療における技術革新
  • 細胞利用がん治療に関与する企業
  • American Association for Cancer Research and ESCs
  • 細胞利用がん治療の将来

第7章 神経疾患対する細胞治療

  • イントロダクション
  • 内因性幹細胞による神経系の再生
  • 神経疾患治療に使用される細胞の種類
  • 神経学用途に対する細胞治療法
  • 細胞治療に適した神経疾患
  • 中枢神経疾患細胞治療の複雑化
  • 神経疾患における細胞治療の治験
  • 中枢神経疾患細胞治療の将来展望

第8章 細胞治療の倫理的・政治的局面

  • イントロダクション
  • 米国におけるヒトES細胞研究の倫理的・政治的局面
  • 世界で利用可能な幹細胞ライン
  • 各国の幹細胞政策
  • 臍帯血に関する倫理問題
  • 参謀治療ツーリズム

第9章 細胞治療の安全・規制局面

  • イントロダクション
  • 細胞治療の安全性問題
  • 細胞・組織製品に対するFDA(米国食品医薬品局)安全基準
  • 米国における臍帯血規制
  • バイオテクノロジー系薬剤に対する規制問題
  • 医療現場における末梢血幹細胞移植用細胞選定装置の規制
  • ヒト細胞・組織に対するFDA規定
  • 異種移植
  • EUにおける細胞治療関連の規制
  • NIH(国立衛生研究所)と幹細胞
  • 細胞治療における治験
  • 幹細胞特許

図表

パートII

第10章 細胞治療の市場および将来展望

  • イントロダクション
  • 市場規模の推定方法
  • 細胞治療市場の有望性
  • 地域別市場規模
  • 細胞治療におけるアンメットニーズ
  • 細胞治療市場発展の推進要因
  • 細胞治療の将来展望
  • 事業戦略

第11章 細胞治療に関与する企業

第12章 学術機関

第13章 参考資料

図表

このページに掲載されている内容は最新版と異なる場合があります。詳細はお問い合わせください。

目次

Summary

This report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. Role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. Current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

The cell-based markets was analyzed for 2011, and projected to 2021.The markets are analyzed according to therapeutic categories, technologies and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer and cardiovascular disorders. Skin and soft tissue repair as well as diabetes mellitus will be other major markets.

The number of companies involved in cell therapy has increased remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 280 of these are profiled in part II of the report along with tabulation of 270 alliances. Of these companies, 154 are involved in stem cells. Profiles of 69 academic institutions in the US involved in cell therapy are also included in part II along with their commercial collaborations. The text is supplemented with 52 Tables and 11 Figures. The bibliography contains 1,050 selected references, which are cited in the text.

Table of Contents

Part I

0. Executive Summary 24

1. Introduction to Cell Therapy 28

  • Introduction 28
  • Historical landmarks of cell therapy 28
  • Interrelationship of cell therapy technologies 30
  • Cells and organ transplantation 30
  • Cells and protein/gene therapy 31
  • Cell therapy and regenerative medicine 32
  • Cells therapy and tissue engineering 32
  • Therapy based on cells involved in disease 33
  • Advantages of therapeutic use of cells 33
  • Cell-based drug delivery 34
  • Cells as vehicles for gene delivery 34
  • Red blood cells as vehicles for drug delivery 34
  • Advantages of cell-based drug delivery 35
  • Limitations of cell-based drug delivery 35

2. Cell Therapy Technologies 38

  • Introduction 38
  • Cell types used for therapy 38
  • Sources of cells 38
  • Xenografts 39
  • Cell lines 39
  • Immortalized cells 39
  • Blood component therapy 39
  • Therapeutic apheresis 39
  • Leukoreduction 40
  • Platelet therapy 40
  • Basic technologies for cell therapy 41
  • Cell culture 41
  • Automated cell culture devices 41
  • Cell culture for adoptive cell therapy 42
  • Observation of stem cell growth and viability 42
  • OpTmizer™ CTS™ T cell expansion tissue culture medium 42
  • Companies involved in cell culture 42
  • Cell sorting 44
  • Flow cytometry 44
  • Applications of flow cytometry 45
  • A dielectrophoretic system for cell separation 45
  • Adult stem cell sorting by identification of surface markers 45
  • ALDESORTER system for isolation of stem cells 46
  • Dynabead technology for cell sorting 46
  • Elutra® Cell Separation System 46
  • Molecular beacons for specific detection and isolation of stem cells 47
  • Multitarget magnetic activated cell sorter 47
  • Nanocytometry 47
  • Scepter™ cytometer 48
  • Companies supplying cell sorters 48
  • Cell analysis 49
  • Cell analyzers 49
  • In vivo cell imaging 50
  • Measuring cell density 50
  • Single-cell gene expression analysis 50
  • Preservation of cells 51
  • Innovations in cryopreservation 52
  • Packaging of cells 53
  • Selective expansion of T cells for immunotherapy 53
  • Cloning and cell therapy 54
  • Techniques for cell manipulation 54
  • Altering function of adult human cells 55
  • Cell-based drug discovery 55
  • Advantages and limitations of cell-based assays for drug discovery 55
  • Advantages and limitations of cell-based toxicity screening 56
  • Quality control of cells for drug discovery 56
  • Companies involved in cell-based drug discovery 56
  • Drug delivery systems for cell therapy 58
  • Intravenous delivery of stem cells 58
  • Intraarterial delivery of stem cells 59
  • Pharmacologically active microcarriers 59
  • Targeted delivery of engineered cells to specific tissues via circulation 60
  • Devices for delivery of cell therapy 60
  • Artificial cells 61
  • Applications of artificial cells 61
  • Cell encapsulation 61
  • Cell-in-a-Box® 62
  • Diffusion capsule for cells 62
  • Encapsulated cell biodelivery 62
  • Therapeutic applications of encapsulated cells 63
  • Nitric oxide delivery by encapsulated cells 64
  • Implantation of microencapulated genetically modified cells 65
  • Ferrofluid microcapsules for tracking with MRI 65
  • Companies involved in encapsulated cell technology 65
  • Electroporation 66
  • Gene therapy 67
  • Cell-mediated gene therapy 67
  • Fibroblasts 67
  • Chondrocyte 68
  • Skeletal muscle cells 68
  • Vascular smooth muscle cells 69
  • Keratinocytes 69
  • Hepatocytes 69
  • Lymphocytes 70
  • Mammalian artificial chromosomes 70
  • In vivo tracking of cells 70
  • Molecular imaging for tracking cells 70
  • MRI technologies for tracking cells 71
  • Superparamagnetic iron oxide nanoparticles as MRI contrast agents 72
  • Visualization of gene expression in vivo by MRI 72
  • Optogenetic monitoring of cell therapies 73
  • Role of nanobiotechnology in development of cell therapy 73
  • Cell transplantation for development of organs 74
  • Cells transplantation and tolerance 74
  • Strategies to improve tolerance of transplanted cells 74
  • Encapsulation to prevent immune rejection 75
  • Prevention of rejection of xenotransplants 75
  • Expansion of allospecific regulatory T cells 75
  • Removal and replacement of pathogenic cells of the body 76
  • Therapeutic leukocytapheresis 76

3. Stem Cells 78

  • Introduction 78
  • Biology of stem cells 79
  • Embryonic stem cells 79
  • Growth and differentiation of ESCs 79
  • Mechanisms of differentiation of ESCs 80
  • Chemical regulation of stem cell differentiation 80
  • In vitro differentiation of hESCs 80
  • SIRT1 regulation during stem cell differentiation 80
  • Regulation of stem cell self-renewal and differentiation 81
  • hESCs for reprogramming human somatic nuclei 81
  • Stem cells differentiation in the pituitary gland 81
  • Influence of microenvironment on ESCs 82
  • Role of genes in differentiation of ESCs 82
  • Global transcription in pluripotent ESCs 82
  • Role of p53 tumor suppressor gene in stem cell differentiation 82
  • Role of Pax3 gene in stem cell differentiation 83
  • Signaling pathways and ESC genes 83
  • Epigenetics of hESCs 84
  • Chromatin as gene regulator for ESC development 84
  • Mechanism of regulation of stem cells for regeneration of body tissues 85
  • Role of microenvironments in the regulation of stem cells 85
  • Regulation and regeneration of intestinal stem cells 85
  • Parthenogenesis and human stem cells 86
  • Uniparental ESCs 87
  • Bone marrow stem cells 87
  • Hematopoietic stem cells 87
  • Role of HSCs in the immune system 89
  • Derivation of HSCs from ESCs 89
  • Mesenchymal stem cells 90
  • Multipotent adult progenitor cells 91
  • Side population (SP) stem cells 92
  • Differentiation of adult stem cells 92
  • Growth and differentiation of HSCs 93
  • Signaling pathways in the growth and differentiation of HSCs 93
  • Mathematical modeling of differentiation of HSCs 94
  • Role of prions in self renewal of HSCs 94
  • Sources of stem cells 95
  • Sources of of human embryonic stem cells 95
  • Nuclear transfer to obtain hESCs 95
  • Direct derivation of hESCs from embryos without nuclear transfer 96
  • Alternative methods of obtaining hESCs 97
  • Establishing hESC lines without destruction of embryo 97
  • Altered nuclear transfer 98
  • Small embryonic-like stem cells (SEL-SCs) 98
  • Advantages and disadvantages of ESCs for transplantation 98
  • Use of ESC cultures as an alternative source of tissue for transplantation 99
  • Spermatogonial stem cells 100
  • Amniotic fluid as a source of stem cells 100
  • Amniotic fluid stem cells for tissue repair and regeneration 101
  • Generation of iPS cells from AF cells 101
  • Placenta as source of stem cells 102
  • Amnion-derived multipotent progenitor cells 102
  • Placenta as a source of HSCs 102
  • Umbilical cord as a source of MSCs 103
  • Umbilical cord blood as source of neonatal stem cells 103
  • Cryopreservation of UCB stem cells 104
  • UCB as source of MSCs 104
  • Applications of UCB 105
  • Advantages of UCB 105
  • Limitations of the use of UCB and measures to address them 106
  • Licensing and patent disputes involving UCB 107
  • Infections following UCB transplants 107
  • Unanswered questions about UCB transplantation 108
  • Companies involved in UCB banking 108
  • UCB banking in the UK 109
  • US national UCB banking system 110
  • Future prospects of UCB as a source of stem cells 111
  • Induced pluripotent stem cells derived from human somatic cells 111
  • Characteristics of iPSCs 112
  • DNA methylation patterns of iPS cells 112
  • iPSCs derived from oocytes through SCNT 112
  • iPSCs derived from skin 113
  • iPSCs derived from blood 113
  • Use of retroviral vectors for generation of iPSCs 114
  • Use of non-integrating viral vectors for generation of iPSCs 114
  • Banks providing patient-specific iPSC lines 115
  • Companies providing iPSCs 116
  • Generation of clinically relevant iPSCs 116
  • Generation of HSCs from iPSCs 117
  • Generation of RBCs from iPSCs 117
  • iPSCs and disease modeling 117
  • iPSCs for patient-specific regenerative medicine 118
  • Concluding remarks about clinical potential of iPSCs 118
  • Induced conditional self-renewing progenitor cells 119
  • Epiblast stem cells 119
  • Comparison of development of human and mouse ESCs 119
  • Conversion of hESCs to mouse ESC-like naïve states 120
  • Sources of adult human stem cells 120
  • Adipose tissue as a source of stem cells 121
  • Intravenous infusion of adipose tissue derived MSCs 121
  • iPSCs derived from adult human adipose stem cells 121
  • Regulation of adipose stem cells differentiation 122
  • Transforming adult adipose stem cells into other cells 122
  • Multipotent stem-like cells derived from vascular endothelial cells 122
  • Skin as a source of stem cells 123
  • Controlling the maturation of embryonic skin stem cells 123
  • Epidermal neural crest stem cells 123
  • Follicle stem cells 123
  • Mesenchymal stem cells in skin 124
  • Regulation of stem cells in hair follicles 124
  • Skin-derived precursor cells 125
  • Regulation of epidermal stem cells by circadian rhythms 125
  • Stem cells in teeth 125
  • Peripheral blood stem cells 126
  • Spleen as a source of adult stem cells 127
  • Search for master stem cells 127
  • Vascular cell platform to self-renew adult HSC 127
  • Adult stem cells vs embryonic stem cells 128
  • Biological differences between adult and embryonic stem cells 128
  • Neural crest stem cells from adult hair follicles 128
  • Transdifferentiation potential of adult stem cells 129
  • Limitations of adult stem cells 130
  • Comparison of human stem cells according to derivation 130
  • VENT cells 131
  • ESC banking 131
  • Stem cell technologies 131
  • Analysis of stem cell growth and differentiation 131
  • Activation of bone marrow stem cells into therapeutic cells 132
  • Role of nitric oxide in stem cell mobilization and differentiation 132
  • Role of natriuretic peptide receptor-C in self-renewal of murine ESCs 132
  • Stem cell biomarkers 133
  • Endoglin as a functional biomarker of HSCs 133
  • STEMPRO® EZChek™ for analysis of biomarkers of hESCs 133
  • SSEA-4 as biomarker of MSCs 133
  • p75NTR as a biomarker to isolate adipose tissue-derived stem cells 134
  • Neural stem cell biomarker 134
  • Protein expression profile as biomarker of stem cells 134
  • Real-time PCR for quantification of protein biomarkers 135
  • Study of stem cell pathways 135
  • Stem cell genomics 135
  • Gene expression in hESCs 135
  • Genomic alterations in cultured hESCs 136
  • Study of transcriptional regulation of stem cell genes 136
  • Casanova gene in zebrafish 137
  • Nanog gene 137
  • Gene inactivation to study hESCs 138
  • RNAi to study gene inactivation in hESCs 138
  • Study of ESC development by inducible RNAi 139
  • Targeting Induced Local Lesions in Genomes 139
  • Homologous recombination of ESCs 139
  • Gene modification in genomes of hESCs and hiPSCs using zinc-finger nuclease 140
  • miRNA and stem cells 140
  • Role of miRNAs in gene regulation during stem cell differentiation 140
  • Influence of miRNA on stem cell formation and maintenance 141
  • Transcriptional regulators of ESCs control miRNA gene expression 142
  • Stem cells and cloning 142
  • Cell nuclear replacement and cloning 142
  • Nuclear transfer and ESCs 142
  • Cloning from differentiated cells 144
  • Cloning mice from adult stem cells 144
  • Creating interspecies stem cells 145
  • Cloned cells for transplantation medicine 145
  • Claims of cloning of hESCs 145
  • hESCs derived by SCNT 147
  • Cytogenetics of embryonic stem cells 147
  • Stem cell proteomics 148
  • Comparative proteomic analysis of somatic cells, iPSCs and ESCs 148
  • hESC phosphoproteome 149
  • Proteomic studies of mesenchymal stem cells 149
  • Proteomic profiling of neural stem cells 149
  • Proteome Biology of Stem Cells Initiative 150
  • Technologies for mobilization, expansion, and engraftment of stem cells 150
  • Chemoattraction of neuronal stem cells through GABA receptor 151
  • Enhancement of HSC engraftment by calcium-sensing receptor 151
  • Ex vivo expansion of human HSCs in culture 151
  • Ex vivo expansion of MSCs 152
  • Ex vivo expansion of UCB cells for transplantation 152
  • Expansion of adult stem cells by activation of Oct4 153
  • Expansion of transduced HSCs in vivo 153
  • Expansion of stem cells in vivo by Notch receptor ligands 153
  • In vivo adipogenesis induced by adipose tissue-derived stem cells 154
  • Selective mobilization of progenitor cells from bone marrow 154
  • Selective Amplification 154
  • Synthetic substrates for ESC growth and expansion 155
  • Technologies for inducing differentiation of stem cells 155
  • Enhancement of stem cell differentiation by Homspera 155
  • Generation of RBCs from HSCs 155
  • Generation of multiple types of WBCs from hESCs and iPSCs 156
  • Growth factor-induced differentiation of MAPCs 156
  • Lineage selection to induce differentiation of hESCs 156
  • Mechanical strain to induce MSC differentiation 157
  • Neurotrophin-mediated survival and differentiation of hESCs 157
  • Synthetic biology and stem cells 157
  • Use of RNAi to expand the plasticity of autologous adult stem cells 158
  • Use of carbohydrate molecules to induce differentiation of stem cells 158
  • Limitations of the currently available stem cell lines in the US 158
  • Stem cell separation 159
  • Stem cell culture 159
  • Culture of hMSCs 160
  • Elimination of contaminating material in stem cell culture 160
  • Long-term maintenance of MSC multipotency in culture 162
  • Nanofiber scaffolds for stem cell culture 162
  • Conversion of stem cells to functioning adipocytes 163
  • Mass production of ESCs 163
  • Promoting survival of dissociated hESCs 163
  • Analysis and characterization of stem cells 164
  • Havesting and identification of EPCs 164
  • Labeling of stem cells 165
  • Labeling, imaging and tracking of stem cells in vivo 165
  • Perfluorocarbon nanoparticles to track therapeutic cells in vivo 165
  • PET imaging for tracking of stem cells 166
  • Project for imaging in stem cell therapy research 166
  • Quantum dots for labeling and imaging of stem cells 166
  • Radiolabeling of MSCs for in vivo tracking 167
  • Superparamagnetic iron oxide nanoparticles for tracking MSCs 167
  • Tracking of transplanted muscle stem cells 167
  • Applications of stem cells 168
  • Commercial development and applications of adult stem cells 168
  • Retrodifferentiation of stem cells 168
  • MultiStem 169
  • Controlling the maintenance process of hematopoietic stem cells 169
  • Self renewal and proliferation of HSCs 169
  • Aging and rejuvenation of HSCs 169
  • Aging and MSCs 170
  • iPSC-based modeling of late-onset age-related diseases 170
  • Peripheral blood stem cell transplantation 170
  • Role of stem cells in regeneration 171
  • Promotion of regeneration by Wnt/beta-catenin signaling 171
  • Stem cell activation for regeneration by using glucocortoids 172
  • Stem cells and human reproduction 172
  • Expansion of spermatogonial stem cells 172
  • Conversion of ESCs into spermatogonial stem cells 172
  • Conversion of stem cells to oocytes 173
  • ESCs for treatment of infertility in women 173
  • Cloning human embryos from oocytes matured in the laboratory 174
  • In utero stem cell transplantation 174
  • Innovations in delivery of stem cells 175
  • Polymeric capsules for stem cell delivery 175
  • Immunological aspects of hESC transplantation 176
  • Immunosuppression to prevent rejection of hESC transplants 176
  • Histocompatibility of hESCs 176
  • Strategies for promoting immune tolerance of hESCs 177
  • Stem cells for organ vascularization 177
  • Activation of EphB4 to enhance angiogenesis by EPCs 178
  • Advantages and limitations of clinical applications of iPSCs 178
  • Advantages and limitations of clinical applications of MSCs 179
  • Biofusion by genetically engineering stem cells 179
  • Stem cell gene therapy 179
  • Combination of gene therapy with nuclear transfer 180
  • Gene delivery to stem cells by artificial chromosome expression 180
  • Genetic manipulation of ESCs 180
  • Genetic engineering of human stem cells for enhancing angiogenesis 181
  • HSCs for gene therapy 181
  • iPSCs for targeted gene correction of α1-antitrypsin deficiency 182
  • Helper-dependent adenoviral vectors for gene transfer in ESCs 182
  • Lentiviral vectors for in vivo gene transfer to stem cells 182
  • Linker based sperm-mediated gene transfer technology 183
  • Mesenchymal stem cells for gene therapy 183
  • Microporation for transfection of MSCs 183
  • Regulation of gene expression for SC-based gene therapy 183
  • Stem cells and in utero gene therapy 184
  • Therapeutic applications for hematopoietic stem cell gene transfer 184
  • The future of hematopoietic stem cell gene therapy 184
  • Stem cell pharmaceutics 185
  • Pharmaceutical manipulation of stem cells 185
  • Antisense approach for preservation and expansion of stem cells 186
  • Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase 186
  • Manipulation of stem cells with growth factors 187
  • Mobilization of stem cells by cytokines/chemokines 189
  • Mobilization of adult human HSCs by use of inhibitors 190
  • Mobilization of stem cells by HYC750 190
  • Mobilization of stem cells by hyperbaric oxygen 191
  • Mobilization by adenoviral vectors expressing angiogenic factors 191
  • Stem cell mobilization by acetylcholine receptor agonists 192
  • Use of parathyroid hormone to increase HSC mobilization 192
  • Use of small molecule compounds for expansion of HSCs 192
  • Role of stem cells in therapeutic effects of drugs 193
  • Stem cells for drug discovery 193
  • Target identification 193
  • High-throughput screening 193
  • Cardiomyocytes derived from hESCs 194
  • ESCs as source of models for drug discovery 194
  • hESC-derived hepatocytes for drug discovery 195
  • Advantages and limitations of use of stem cells for drug discovery 196
  • Stem cells for drug delivery 196
  • Toxicology and drug safety studies using ESCs versus other cells 197
  • Future challenges for stem cell technologies 199
  • Generation of patient-specific pluripotent stem cells 199
  • Hybrid embryos/cybrids for stem cell research 200
  • In vivo study of human hemopoietic stem cells 201
  • Inhibition of stem cell-derived teratoma formation by small molecules 201
  • Markers for characterizing hESC lines 201
  • MBD3-deficient ESC line 202
  • Research into plasticity of stem cells from adults 202
  • Stem cell biology and cancer 202
  • Stem cells and aging 203
  • Stem cells in space 204
  • Study of the molecular mechanism of cell differentiation 204
  • Switch of stem-cell function from activators to repressors 205
  • Stem cell research at academic centers 205
  • International Regulome Consortium 207
  • Companies involved in stem cell technologies 207
  • Concluding remarks about stem cells 212
  • Challenges and future prospects of stem cell research 212

4. Clinical Applications of Cell Therapy 214

  • Introduction 214
  • Cell therapy for hematological disorders 214
  • Transplantation of autologous hematopoietic stem cells 214
  • Hemophilias 214
  • Ex vivo cell/gene therapy of hemophilia B 215
  • Cell/gene therapy of hemophilia A 215
  • Hematopoietic stem cell therapy for thrombocytopenia 216
  • Stem cell transplant for sickle cell anemia 216
  • Treatment of chronic acquired anemias 217
  • Implantation of genetically engineered HSCs to deliver rhEpo 217
  • Drugs acting on stem cells for treatment of anemia 217
  • Stem cell therapy of hemoglobinopathies 218
  • Stem cells for treatment of immunoglobulin-light chain amyloidosis 218
  • Future prospects of cell therapy of hematological disorders 218
  • Cell therapy for immunological disorders 219
  • Role of dendritic cells in the immune system 219
  • Modifying immune responses of DCs by vaccination with lipiodol-siRNA mixtures 219
  • Potential of MSCs as therapy for immune-mediated diseases 220
  • Stem cell therapy of chronic granulomatous disease 220
  • Stem cell therapy of X-linked severe combined immunodeficiency 221
  • Stem cell therapy of autoimmune disorders 221
  • Wiskott-Aldrich Syndrome 221
  • Treatment of rheumatoid arthritis with stem cells 222
  • Treatment of Crohn's disease with stem cells 222
  • Stem cell transplants for scleroderma 222
  • Role of T Cells in immunological disorders 223
  • Autologous T cells from adult stem cells 224
  • Cell therapy for graft vs host disease 224
  • MSCs for GVHD 225
  • Cell therapy for viral infections 225
  • T-cell therapy for CMV 225
  • T-cell therapy for HIV infection 226
  • T-cell immunity by Overlapping Peptide-pulsed Autologous Cells 227
  • Anti-HIV ribozyme delivered in hematopoietic progenitor cells 227
  • Dendritic-cell targeted DNA vaccine for HIV 227
  • Cell therapy of lysosomal storage diseases 227
  • Niemann-Pick disease 228
  • Gaucher's disease 229
  • Fabry's disease 229
  • Cell therapy for diabetes mellitus 229
  • Limitations of current treatment 230
  • Limitations of insulin therapy for diabetes mellitus 230
  • Limitations of pancreatic transplantation 231
  • Islet cell transplantation 231
  • Autologous pancreatic islet cell transplantation in chronic pancreatitis 231
  • Clinical trials of pancreatic islet cell transplants for diabetes 232
  • Drawbacks of islet cell therapy 232
  • Use of an antioxidant peptide to improve islet cell transplantation 233
  • Cdk-6 and cyclin D1 enhance human beta cell replication and function 233
  • Devices for delivery of therapeutic cells in diabetes 234
  • Monitoring of islet cell transplants with MRI 234
  • Concluding remarks about allogeneic islet transplantation for diabetes 234
  • Encapsulation of insulin producing cells 235
  • Encapsulated porcine pancreatic islet cells for pancreas 235
  • Encapsulated insulinoma cells 235
  • Magnetocapsule enables imaging/tracking of islet cell transplants 236
  • Islet precursor cells 236
  • Dedifferentiation of Β cells to promote regeneration 237
  • Pharmacological approaches for Β cell regeneration 237
  • Xenotransplantation of embryonic pancreatic tissue 238
  • Non-pancreatic tissues for generation of insulin-producing cells 238
  • Exploiting maternal microchimerism to treat diabetes in the child 238
  • Bio-artificial substitutes for pancreas 239
  • Role of stem cells in the treatment of diabetes 239
  • Embryonic stem cells for diabetes 239
  • HSC transplantation to supplement immunosuppressant therapy 241
  • Insulin-producing cells derived from UCB stem cells 241
  • iPSc for diabetes 241
  • Pancreatic stem cells 242
  • Stem cell injection into portal vein of diabetic patients 242
  • Conversion of progenitor cells into insulin-producing cells 243
  • Human neural progenitor cells converted into insulin-producing cells 243
  • Isolation of islet progenitor cells 243
  • Pancreatic progenitor cells 243
  • Dendritic cell-based therapy for type 1 diabetes 244
  • Vaccine for diabetes 244
  • Gene therapy in diabetes 244
  • Viral vectors for gene therapy of diabetes 245
  • Genetically engineered dendritic cells 245
  • Genetically altered liver cells 245
  • Genetically modified stem cells 246
  • Companies developing cell therapy for diabetes 246
  • Concluding remarks about cell and gene therapy of diabetes 247
  • Cell therapy of gastrointestinal disorders 248
  • Inflammatory bowel disease 248
  • Cell therapy for liver disorders 249
  • Types of cells used for hepatic disorders 249
  • Methods of delivery of cells for hepatic disorders 250
  • Bioartificial liver 250
  • Hepatocyte-based artificial liver 250
  • Extracorporeal Liver Assist Device 250
  • Limitations of bioartificial liver 251
  • Proliferating cell-based bioartificial liver 251
  • Stem cells for hepatic disorders 251
  • Deriving hepatocytes from commercially available hMSCs 252
  • Implantation of hepatic cells derived from hMSCs of adipose tissue 252
  • Heterologous adult liver progenitor cells 253
  • Liver stem cell culture 253
  • MSC derived molecules for reversing hepatic failure 253
  • Cell-based gene therapy for liver disorders 254
  • Transplantation of genetically modified fibroblasts 254
  • Transplantation of genetically modified hepatocytes 254
  • Genetically modified hematopoietic stem cells 255
  • iPSCs derived from somatic cells for liver regeneration 255
  • Hepatocyte-like cells derived from human parthenogenetic stem cells 255
  • Clinical applications 256
  • Future prospects of cell-based therapy of hepatic disorders 256
  • Cell therapy of renal disorders 257
  • Bioartificial kidney 257
  • Cell-based repair for vascular access failure in renal disease 258
  • Mesangial cell therapy for glomerular disease 258
  • Stem cells for renal disease 258
  • Role of stem cells in renal repair 259
  • Bone marrow stem cells for renal disease 259
  • Human amniotic fluid stem cells for renal regeneration 259
  • MSC therapy for renal disease 260
  • Cell therapy for pulmonary disorders 260
  • Delivery of cell therapy for pumonary disorders 260
  • Intratracheal injection of cells for pulmonary hypoplasia 260
  • Role of stem cells in pulmonary disorders 261
  • Lung stem cells 261
  • Lung tissue regeneration from stem cells 261
  • Role of stem cells in construction of the Cyberlung 262
  • Respiratory epithelial cells derived from UCB stem cells 262
  • Respiratory epithelial cells derived from hESCs 262
  • Lung tissue engineering with adipose stromal cells 263
  • Cell-based tissue-engineering of airway 263
  • Pulmonary disorders that can be treatable with stem cells 263
  • Acute lung injury and ARDS treated with MSCs 264
  • Bronchopulmonary dysplasia treated with MSCs 265
  • Chronic obstructive pulmonary disease treated with MSCs 265
  • Cystic fibrosis treatment with genetically engineered MSCs 265
  • Lung regeneration by integrin α6Β4-expressing alveolar epithelial cell 266
  • Pulmonary arterial hypertension treatment with EPCs 266
  • Cell therapy for disorders of bones and joints 267
  • Repair of fractures and bone defects 267
  • Adult stem cells for bone grafting 268
  • Bone regeneration by human very small embryonic-like (hVSEL) cells 268
  • Cell therapy for osteonecrosis 268
  • Cell therapy for radionecrosis 268
  • Cell therapy for cervical vertebral interbody fusion 269
  • Cell-mediated gene therapy for bone regeneration 269
  • ESCs for bone repair 269
  • hiPSCs for engineering personalized bone grafts 269
  • Intrauterine use of MSCs for osteogenesis imperfecta 269
  • In vivo bone engineering as an alternative to cell transplantation 270
  • In vivo differentiation of pluripotent stem cells for bone regeneration 270
  • MSCs for repair of bone defects 270
  • MSCs for repair of bone fractures 273
  • Osteocel 274
  • Stem cells for repairing skull defects 274
  • Stem cell-based bone tissue engineering 274
  • Spinal fusion using stem cell-based bone grafts 275
  • Osteoarthritis and other injuries to the joints 276
  • Mosaicplasty 276
  • Autologous cultured chondrocytes 276
  • Autologous intervertebral disc chondrocyte transplantation 277
  • Cartilage repair by genetically modified fibroblasts expressing TGF-Β 278
  • Cartilage generation from stem cells 279
  • Cartilage engineering from iPSCs 280
  • Repair of osteonecrosis by bone marrow derived MSCs 280
  • Role of cell therapy in repair of knee cartilage injuries 281
  • Chondrocyte cell therapy 282
  • Meniscus-derived stem cells 282
  • Nanobiotechnology scaffolds for MSC-based cartilage reconstruction 282
  • Role of cells in the repair of anterior cruciate ligament injury 283
  • Autologous tenocyte implantation in rotator cuff injury repair 283
  • Platelet injection for tennis elbow 284
  • Cell therapy of rheumatoid arthritis 284
  • Cell therapy for diseases of the eye 285
  • Cell therapy for corneal repair 285
  • Stem cell therapy for limbal stem cell deficiency 286
  • Role of stem cells in fibrosis following eye injury 287
  • Stem cell transplantation for radiation sickness 287
  • MSCs for treatment of radiation damage to the bone 287
  • MSCs for regeneration of ovaries following radiotherapy damage 288
  • Cell therapy for wound healing 288
  • Cells to form skin substitutes for healing ulcers 288
  • CellSpray for wound repair 289
  • Cell therapy for burns 290
  • Closure of incisions with laser guns and cells 290
  • Genetically engineered keratinocytes for wound repair 291
  • Stem cells for skin regeneration 291
  • Follicular stem cells for skin and wound repair 291
  • MSCs for wound healing 292
  • Regeneration of aging skin by adipose-derived stem cells 292
  • Reprogramming autologous stem cells for wound regeneration 292
  • Role of amniotic fluid MSCs in repair of fetal wounds 292
  • Concluding remarks on regeneration of skin by stem cells 293
  • Cell therapy for regeneration 293
  • Stem cells for regenerating organs 293
  • Umbilical cord blood for regeneration 294
  • Role of stem cells in regeneration of esophageal epithelium 294
  • Cell therapy for regeneration of muscle wasting 295
  • Role of cells in tissue engineering and reconstructive surgery 295
  • Scaffolds for tissue engineering 295
  • Improving vascularization of engineered tissues 296
  • Reconstruction of vasculature 296
  • Repair of aging skin by injecting autologous fibroblasts 297
  • Enhancing vascularization by combining cell and gene therapy 297
  • Nanobiotechnology applied to cells for tissue engineering 297
  • Choosing cells for tissue engineering 298
  • Stem cells for tissue repair 298
  • ESCs vs adult SCs for tissue engineering 299
  • Use of adult MSCs for tissue engineering 300
  • Stem cells for tissue engineering of various organs 300
  • Breast reconstruction by adipose tissue-derived stem cells 300
  • Engineering of healthy living teeth from stem cells 300
  • Intra-uterine repair of congenital defects using amniotic fluid MSCs 301
  • Skin regeneration by stem cells as an alternative to face transplant 302
  • Tissue engineering of bone by stem cells 302
  • Cell-based tissue engineering in genitourinary system 303
  • Urinary incontinence 303
  • Tissue engineering of urinary bladder 304
  • Label retaining urothelial cells for bladder repair 305
  • MSCs for bladder repair 305
  • Tissue-engineering of urethra using autologous cells 305
  • Repair of the pelvic floor with stem cells from the uterus 306
  • Reconstruction of vagina from stem cells 306
  • Reconstruction of cartilage for repair of craniofacial defects 306
  • Intraoperative cell therapy 307
  • Cell therapy for rejuvenation 307
  • Cell therapy for performance enhancement in sports 307
  • Application of stem cells in veterinary medicine 308
  • Use of stem cells to repair tendon injuries 308
  • Stem cells for spinal cord injury in dogs 309

5. Cell Therapy for Cardiovascular Disorders 310

  • Introduction to cardiovascular disorders 310
  • Limitations of current therapies for myocardial ischemic disease 310
  • Types of cell therapy for cardiovascular disorders 310
  • Cell-mediated immune modulation for chronic heart disease 312
  • Inducing the proliferation of cardiomyocytes 312
  • Pericardial origin of colony-forming units 312
  • Role of splenic myocytes in repair of the injured heart 313
  • Reprogramming of fibroblasts into functional cardiomyocytes 313
  • Stem cell-based therapies for cardiac diseases 314
  • Human cardiovascular progenitor cells 314
  • Human pluripotent stem cell-derived cardiomyocytes 315
  • Role of the SDF-1-CXCR4 axis in therapies for myocardial ischemia 315
  • Small molecules to enhance myocardial repair by stem cells 315
  • Cell therapy for atherosclerotic coronary artery disease 315
  • MyoCell™ (Bioheart) 316
  • Cardiac stem cells 316
  • Cardiomyocytes derived from epicardium 317
  • Methods of delivery of cells to the heart 318
  • Cellular cardiomyoplasty 318
  • IGF-1 delivery by nanofibers to improve cell therapy for MI 318
  • Non-invasive delivery of cells to the heart by Morph®guide catheter 318
  • Cell therapy for cardiac revascularization 319
  • Transplantation of cardiac progenitor cells for revascularization of myocardium 319
  • Stem cells to prevent restenosis after coronary angioplasty 319
  • Role of cells in cardiac tissue repair 320
  • Modulation of cardiac macrophages for repair of infarct 320
  • Transplantation of myoblasts for myocardial infarction 320
  • Patching myocardial infarction with fibroblast culture 321
  • Cardiac repair with myoendothelial cells from skeletal muscle 321
  • Myocardial tissue engineering 322
  • Role of stem cells in repair of the heart 323
  • Role of stem cells in cardiac regeneration following injury 323
  • Cardiomyocytes derived from adult skin cells 323
  • Cardiomyocytes derived from ESCs 323
  • Cardiomyocyte differentiation from hIPSCs 325
  • Studies to identify subsets of progenitor cells suitable for cardiac repair 325
  • Technologies for preparation of stem cells for cardiovascular therapy 326
  • Pravastatin for expansion of endogenous progenitor and stem cells 326
  • Cytokine preconditioning of human fetal liver CD133+ SCs 326
  • Expansion of adult cardiac stem cells for transplantation 326
  • Role of MSCs in growth of CSCs 327
  • Role of ESCs in repair of the heart 327
  • ESC transplantation for tumor-free repair of the heart 328
  • Transplantation of stem cells for myocardial infarction 328
  • Autologous bone marrow-derived stem cell therapeutics 328
  • Autologous bone marrow-derived mesenchymal precursor stem cells 329
  • Intracoronary infusion of mobilized peripheral blood stem cells 329
  • Transplantation of cord blood stem cells 330
  • Transplantation of hESCs 330
  • Transplantation of HSCs 331
  • Transplantation of autologous angiogenic cell precursors 331
  • Transplantation of adipose-derived stem cells 331
  • Transplantation of bone marrow-derived cells for myocardial infarct 332
  • Transplantation of human umbilical cord perivascular cells 333
  • Transplantation of endothelial cells 334
  • Transplantation of cardiomyocytes differentiated from hESCs 334
  • Stem cell therapy for cardiac regeneration 334
  • Regeneration of the chronic myocardial infarcts by HSC therapy 335
  • Human mesenchymal stem cells for cardiac regeneration 335
  • In vivo tracking of MSCs transplanted in the heart 336
  • MSCs for hibernating myocardium 336
  • Simultaneous transplantation of MSCs and skeletal myoblasts 337
  • Transplantation of genetically modified cells 337
  • Transplantation of genetically modified MSCs 337
  • Transplantation of cells secreting vascular endothelial growth factor 337
  • Transplantation of genetically modified bone marrow stem cells 338
  • Cell transplantation for congestive heart failure 338
  • AngioCell gene therapy for congestive heart failure 339
  • Injection of adult stem cells for CHF 339
  • Intracoronary infusion of cardiac stem cells 340
  • Myoblasts for treatment of congestive heart failure 340
  • Stem cell therapy for dilated cardiac myopathy 340
  • Role of cell therapy in cardiac arrhythmias 341
  • Prevention of myoblast-induced arrhythmias by genetic engineering 341
  • Stem cells as biological pacemakers 341
  • Stem cells for cardiac arrythmias 342
  • Ventricular tachycardia 343
  • ESCs for correction of congenital heart defects 343
  • Cardiac progenitors cells for treatment of heart disease 344
  • Autologus stem cells for chronic myocardial ischemia 344
  • Role of cells in cardiovascular tissue engineering 345
  • Construction of blood vessels with cells 345
  • Engineered arteries for bypass grafts 345
  • Fetal cardiomyocytes seeding in tissue-engineered cardiac grafts 345
  • Targeted delivery of endothelial progenitor cells labeled with nanoparticles 346
  • UCB progenitor cells for engineering heart valves 346
  • Cell-based in vitro regeneration of heart for transplantation 346
  • Cell therapy for peripheral vascular disease 346
  • ALD-301 347
  • Cell/gene therapy for PVD 347
  • Cell therapy for CLI in diabetics 347
  • Colony stimulating factors for enhancing peripheral blood stem cells 347
  • Intramuscular autologous bone marrow cells 348
  • Ixmyelocel-T cell therapy for critical limb ischemia 348
  • Stem cell-coated vascular grafts for femoral-tibial arterial bypass 349
  • Clinical trials of cell therapy in cardiovascular disease 349
  • Mechanism of the benefit of cell therapy for heart disease 351
  • A critical evaluation of cell therapy for heart disease 352
  • Publications of clinical trials of cell therapy for CVD 352
  • Current status of cell therapy for cardiovascular disease 353
  • Future directions for cell therapy of CVD 353
  • Prospects of adult stem cell therapy for repair of heart 354
  • Combination of cells with biomedical scaffolds 354
  • Regeneration of cardiomyocytes without use of cardiac stem cells 355

6. Cell Therapy for Cancer 356

  • Introduction 356
  • Cell therapy technologies for cancer 356
  • Cell-based delivery of anticancer therapy 357
  • Cellular immunotherapy for cancer 357
  • Treatments for cancer by ex vivo mobilization of immune cells 358
  • Granulocytes as anticancer agents 358
  • Neutrophil granulocytes in antibody-based immunotherapy of cancer 359
  • Cancer vaccines 359
  • Autologous tumor cell vaccines 359
  • BIOVAXID 359
  • OncoVAX 360
  • Tumor cells treated with dinitrophenyl 360
  • Vaccines that simultaneously target different cancer antigens 360
  • Gene modified cancer cells vaccines 360
  • GVAX cancer vaccines 361
  • K562/GM-CSF 361
  • Active immunotherapy based on antigen specific to the tumor 362
  • The use of dendritic cells for cancer vaccination 362
  • Autologous dendritic cells loaded ex vivo with telomerase mRNA 362
  • Dendritic cell-targeted protein vaccines 363
  • Dendritic/tumor cell fusion 363
  • Genetically modified dendritic cells 363
  • In vivo manipulation of dendritic cells 364
  • Preclinical and clinical studies with DC vaccines 364
  • Vaccines based on dendritic cell-derived exosomes 365
  • Limitations of DC vaccines for cancer 365
  • Future developments to enhance clinical efficacy of DC vaccines 365
  • Lymphocyte-based cancer therapies 367
  • Adoptive cell therapy 367
  • Chimeric antigen receptor T cells 368
  • Combination of antiangiogenic agents with ACT 370
  • Expansion of antigen-specific cytotoxic T lymphocytes 370
  • Genetic engineering of tumor cells to activate T helper cells 370
  • CD8+ T cells for use in tumor immunotherapy 371
  • Tumor infiltrating lymphocytes 371
  • Hybrid cell vaccination 372
  • Chemoimmunotherapy 372
  • Stem cell-based anticancer therapies 372
  • Stem cell transplantation in cancer 372
  • Peripheral blood stem cell transplantation 373
  • Stem cell transplantation for hematological malignancies 375
  • Long-term results of HSC transplantation 376
  • Prediction of T-cell reconstitution after HSC transplantation 376
  • HSC transplantation followed by GM-CSF-secreting cell vaccines 376
  • HSC transplantation for renal cell cancer 377
  • Complications of stem cell transplants in cancer 377
  • Graft-versus-host disease (GVHD) 377
  • Delayed immune reconstitution leading to viral infections and relapse 378
  • Tumor cell contamination 378
  • Neurological complications 378
  • Hepatic veno-occlusive disease 378
  • Current status of the safety of allogeneic HSC transplantation 379
  • Complications of PBSC transplantation in children 379
  • Role of MSCs in cancer 380
  • MSC-mediated delivery of anticancer therapeutics 380
  • Nonmyeloablative allogeneic hematopoietic stem cell transplantation 380
  • Umbilical cord blood transplant for leukemia 381
  • hESC-derived NK cells for treatment of cancer 382
  • ESC vaccine for prevention of lung cancer 382
  • Genetic modification of stem cells for cancer therapy 382
  • Genetic modification of hematopoietic stem cells 382
  • Use of hematopoietic stem cells to deliver suicide genes to tumors 383
  • Delivery of anticancer agents by genetically engineered MSCs 383
  • Mesenchymal progenitor cells for delivery of oncolytic adenoviruses 384
  • Genetically modified NSCs for treatment of neuroblastoma 384
  • Innovations in cell-based therapy of cancer 385
  • Use of immortalized cells 385
  • Cancer therapy based on natural killer cells 385
  • Cytokine-induced killer cells 385
  • Mesothelin as a target for cancer immunotherapy 385
  • Nanomagnets for targeted cell-based cancer gene therapy 386
  • Implantation of genetically modified encapsulated cells for anticancer therapy 386
  • Antiangiogenesis therapy by implantation of microencapsulated cells 386
  • Recombinant tumor cells secreting fusion protein 386
  • A device for filtering cancer and stem cells in the blood 387
  • Cancer stem cells 387
  • Role of integrative nuclear signaling in stem cell development 388
  • Cancer stem cell markers 388
  • Breast cancer stem cells 388
  • Role of intestinal stem cells in intestinal polyposis 389
  • Role of endothelial progenitor cells in tumor angiogenesis 389
  • Role of cancer stem cells in metastases 390
  • Therapeutic implications of cancer stem cells 390
  • Targeting cancer stem cells in leukemia 391
  • Targeting cancer stem cells in ovarian cancer 391
  • Targeting cancer stem cells to screen anticancer drugs 391
  • Companies involved in cell-based cancer therapy 392
  • American Association for Cancer Research and ESCs 393
  • Future of cell-based immunotherapy for cancer 394

7. Cell Therapy for Neurological Disorders 396

  • Introduction 396
  • Regeneration of the nervous system by endogenous stem cells 396
  • Molecular mechanism of neurogenesis 396
  • Generation of neurons from astroglia 397
  • In vivo cell replacement therapy by locally induced neural progenitor cells 397
  • Types of cells used for treatment of neurological disorders 398
  • Activated T lymphocytes 398
  • Differentiation of placenta-derived multipotent cells into neurons 398
  • Mesenchymal stem cells induced to secrete neurotrophic factors 399
  • Neural stem cells 399
  • Development of human CNS stem cells 399
  • Distinction between NSCs and intermediate neural progenitors 400
  • Embryonic stem cell-derived neurogenesis 400
  • Fusion of NSCs with endogenous neurons 401
  • Induction of NSCs from hESCs 401
  • Mechanism of migration of NSCs to sites of CNS injury 402
  • Monitoring of implanted NSCs labeled with nanoparticles 403
  • Neural progenitor cells 403
  • Neural stem cells as therapeutic delivery vehicles 405
  • Neural stem cells in the subventricular zone of the brain 405
  • Oligodendrocyte progenitor cells 405
  • Promotion of neural stem cells expansion by betacellulin 405
  • Proteomics of neural stem cells 406
  • Regulation of neural stem cells in the brain 406
  • Role of CSF proteins in regulation of neural progenitor cells 407
  • Sequencing the transcriptomes of neural stem cells 408
  • Study of neural differentiation of hESCs by NeuroStem Chip 408
  • Transformation of neural stem cells into other cell types 408
  • Use of epidermal neural crest stem cells for neurological disorders 408
  • Stem cell transplantation in the CNS 409
  • Development of CNS cells from non-CNS stem cells 409
  • Expansion of adult human neural progenitors 410
  • Hair-follicle stem cells for neural repair 410
  • Neurospheres 410
  • Stem cells from olfactory epithelium for transplantation in the CNS 411
  • Stem cells from human umbilical cord blood for CNS disorders 411
  • Choroid plexus cells for transplantation 411
  • Dental pulp cells for neuroprotection 412
  • Derivation of CNS cells from peripheral nervous system 412
  • Fetal tissue transplants 412
  • Immortalized cells for CNS disorders 413
  • Laboratory mice with human brain cells 413
  • Olfactory ensheathing cells for CNS repair 414
  • Ideal cells for transplantation into the nervous system 414
  • Cell therapy techniques for neurological applications 414
  • Carbon nanotubes to aid stem cell therapy of neurological disorders 414
  • Cells used for gene therapy of neurological disorders 415
  • Fibroblasts 415
  • Stem cells 415
  • Neuronal cells 416
  • Immortalized neural progenitor cells 416
  • Astrocytes 416
  • Cerebral endothelial cells 417
  • Human retinal pigmented epithelial cells 417
  • Enhancement of growth of stem cells in the brain by drugs 417
  • C3-induced differentiation and migration of NPC for repair of the brain 418
  • Stem cell therapies of neurological disorders combined with HBO 419
  • hESCs for CNS repair 419
  • Methods of delivery of cells to the CNS 420
  • Engineered stem cells for drug delivery to the brain 420
  • Neuronal differentiation of stem cells 420
  • Stem cells preparations for CNS disorders 421
  • Tracking of stem cells in the CNS by nanoparticles and MRI 422
  • Use of neural stem cells to construct the blood brain barrier 422
  • Encapsulated cells 423
  • CNS neotissue implant 423
  • Intrathecal delivery of stem cells 423
  • CNS delivery of cells by catheters 424
  • Intravascular administration 424
  • Neurological disorders amenable to cell therapy 425
  • Neuroprotection by cell therapy 425
  • Cells secreting neuroprotective substances 425
  • Stem cells for neuroprotection 426
  • Neuroprotection by intravenous administration of HSCs 426
  • Human UCB-derived stem cells for the aging brain 426
  • hESC transplantation to prevent cognitive impairment from radiation 426
  • Neurodegenerative disorders 427
  • MSCs for therapy of neurodegenerative disorders 427
  • Role of stem cells in neurodegenerative disorders 428
  • Role of NSCs in disorders associated with aging brain 429
  • NSCs for improving memory 429
  • Parkinson's disease 430
  • Cell therapies for PD 430
  • Origin and fate of dopamine neurons 431
  • Human dopaminergic neurons for PD 431
  • Graft survival-enhancing drugs 432
  • Xenografting porcine fetal neurons 432
  • Encapsulated cells for PD 433
  • Stem cell transplantation in animal models of PD 433
  • Trials of stem cell transplantation in PD patients 435
  • Stem cells for production of glial derived neurotrophic factor 436
  • Potential of regeneration of endogenous stem cells in PD 436
  • Human retinal pigment epithelium cells for PD 437
  • Tumorigenic potential of transplantated dopaminergic hESCs 437
  • Transplantation of embryonic medial ganglionic eminence cells 438
  • Delivery of cells for PD 438
  • MSCs for multiple system atrophy 438
  • Cell therapy for Huntington's disease 439
  • Fetal striatal cell transplantation 439
  • Transplantation of encapsulated porcine choroids plexus cells 439
  • iPSCs for HD 440
  • Mobilization of endogenous neural progenitor cells in HD 440
  • Cell therapy for Alzheimer's disease 440
  • Choroid plexus epithelial cells for AD 440
  • Implantation of genetically engineered cells producing NGF 441
  • Implantation of stem cells derived from the skin 441
  • Neural stem cell implantation for Alzheimer's disease 441
  • Cell therapy for amyotrophic lateral sclerosis 442
  • Stem cell techniques for study of ALS 442
  • Use of stem cells for ALS 443
  • Transplantation of glial restricted precursors in ALS 444
  • Stem cell-based drug discovery for ALS 445
  • Cell therapy for demyelinating disorders 445
  • Autologous bone marrow stem cell therapy for multiple sclerosis 446
  • ESCs for remyelination 446
  • Fusokine method of personalized cell therapy of MS 447
  • Genetically engineered macrophages expressing NaV1.5 447
  • Hematopoietic stem cell transplantation for MS 447
  • Mechanism of repair of demyelination after NSC transplantation 448
  • MSCs for multiple sclerosis 448
  • Neural progenitor cells for neuroprotection in MS 449
  • T cell-based personalized vaccine for MS 449
  • Stem cells for chronic inflammatory demyelinating polyneuropathy 449
  • Stem cell transplantation for Pelizaeus-Merzbacher disease 450
  • X-linked adrenoleukodystrophy 450
  • Cell therapy of stroke 450
  • Adult stem cell therapy in stroke 451
  • Implantation of genetically programmed ESCs 452
  • Intravenous infusion of MSCs 452
  • Intravenous infusion of human UCB stem cells 453
  • Intracerebral administration of human adipose tissue stromal cells 454
  • Neural stem cell therapy for stroke 454
  • Transplantation of encapsulated porcine choroids plexus 455
  • Transplantation of fetal porcine cells 455
  • Role of cell therapy in management of stroke according to stage 456
  • Clinical trials of cell therapy for stroke 456
  • Future of cell therapy for stroke 457
  • Cell therapy of traumatic brain injury 458
  • Cell/gene therapy for TBI 459
  • Clinical trials of autologous stem cell therapy for TBI 459
  • Limitations of stem cell therapy for acute TBI 460
  • Improving the microenvironments of transplanted cells in TBI 460
  • Cell therapy for spinal cord injury 460
  • Autoimmune T cells against CNS myelin-associated peptide 461
  • Fetal neural grafts for SCI 461
  • Olfactory-ensheathing cells for SCI 461
  • Oligodendrocyte precursor cells for treatment of SCI 462
  • Schwann cell transplants for SCI 462
  • Transplantation of glial cells for SCI 462
  • Stem cells for SCI 462
  • Bone marrow stem cells for SCI 463
  • Embryonic stem cells for SCI 463
  • Transplantation of induced pluripotent stem cells in SCI 464
  • Transplantation of MSCs for SCI 464
  • Transplantation of NSCs for SCI 464
  • Transplantation of human dental pulp stem cells 465
  • Transdifferentiation of BM stem cells into cholinergic neurons for SCI 465
  • Evaluation of experimental studies of stem cell transplantation in SCI 466
  • Spinal stem cells for treatment of ischemic injury of spinal cord 466
  • Combined approaches for regeneration in SCI 467
  • Combined cell/gene therapy for SCI 467
  • Delivery of cells in SCI 467
  • Intrathecal injection of cells labeled with magnetic nanoparticles 468
  • Intravenous injection of stem cells for spinal cord repair 468
  • Clinical applications of stem cells for SCI 468
  • Autologous bone marrow cell transplantation for SCI 468
  • Cell therapy of syringomyelia 469
  • Cell therapy for neurogenetic disorders 469
  • Hurler's syndrome treated with stem cells 469
  • Krabbe's disease treated with UCB stem cells 470
  • Krabbe's disease treated with combination of cell and gene therapy 470
  • Mitochondrial encephalomyopathies treated with stem cells 471
  • Sanfilippo syndrome type B treated with UCB stem cells 471
  • Cell therapy for lysosomal storage disorders 471
  • Cell therapy for Batten disease 471
  • Cell/gene therapy for Farber's disease 472
  • Genetically modified HSCs for metachromatic leukodystrophy 472
  • Neural stem cells for lysosomal storage disorders 473
  • Cell therapy of epilepsy 473
  • Cell therapy of posttraumatic epilepsy 473
  • Cell therapy for temporal lobe epilepsy 474
  • Cell therapy for pharmacoresistant epilepsies 474
  • Cell therapy for developmental neurological disorders 475
  • Cell therapy for cerebral palsy 475
  • Cell-based therapies for malignant brain tumors 476
  • Bone morphogenetic protein for inhibition of glioblastoma multiforme 476
  • Dendritic cell therapy for brain tumors 476
  • Encapsulated cells for brain tumors 477
  • Immunotherapy of GBM targeting cancer stem cells 477
  • Mesenchymal stem cells for the treatment of gliomas 478
  • Neural stem cells for drug/gene delivery to brain tumors 478
  • Role of cancer stem cells in resistance to radiotherapy 479
  • Stem cell-based therapy targeting EGFR in GBM 480
  • Targeting stem cells in brain tumors 480
  • Clinical trials of cell therapy of glioblastoma multiforme 480
  • Cell therapy for muscle disorders 481
  • Duchenne muscular dystrophy 481
  • Combination of cell and pharmacotherapy for DMD 481
  • Myoblast transplant for DMD 482
  • Myoblast-based gene transfer 482
  • Myoblasts lacking the MyoD gene 482
  • Myoblast injection for treatment of other muscular dystrophies 483
  • Role of satellite cells in the treatment of DMD 483
  • Stem cells for DMD 484
  • Wnt7a treatment for DMD 485
  • Cell therapy for autism 485
  • Management of chronic intractable pain by cell therapy 486
  • Implantation of chromaffin cells 486
  • Role of stem cells in management of pain 487
  • Implantation of astrocytes secreting enkephalin 487
  • Cells for delivery of antinociceptive molecules 487
  • Implantation of genetically engineered cells 488
  • Cell therapy for low back pain 488
  • Cell therapy for neuroendocrine disorders 488
  • Pituitary stem cells 488
  • Cell therapy for retinal degenerative disorders 489
  • Adipose-derived stem cells for retinal degeneration 490
  • Delivery of CNTF by encapsulated cell intraocular implants 490
  • ESCs for retinal degenerative disorders 490
  • Genetically engineered retinal pigmented epithelial cell lines 491
  • hESC-derived RPE cells for macular dystrophy 491
  • Human retinal stem cells 491
  • iPSCs for AMD 492
  • Neuroprotective effect of neural progenitor cell transplantation 492
  • Stem cell transplantation in the retina 492
  • Combining cell and gene therapies for retinal disorders 493
  • Stem cell therapy for hearing loss 493
  • Cell thery for peripheral nerve lesions 494
  • Cell transplants for peripheral nerve injuries 494
  • Role of adipose-derived stem cells in peripheral nerve regeneration 494
  • Treatment of diabetic neuropathy with endothelial progenitor cells 495
  • Complications of cell therapy of neurological disorders 495
  • Tumor formation after CNS transplantation of stem cells 495
  • Uncontrolled differentiation of implanted cells 495
  • Donor stem cell-derived brain tumor 496
  • Tumorigenicity of ESC-derived retinal progenitor cells 496
  • Clinical trials of cell therapy in neurological disorders 496
  • Future prospects for cell therapy of CNS disorders 498

8. Ethical, Legal and Political Aspects of Cell therapy 500

  • Introduction 500
  • Political and ethical aspects of hESC research in the US 500
  • Ethical issues concerning fetal tissues 500
  • Morality and hESC research 500
  • Opponents of hESC research in the US 501
  • Use of hESCs in NIH-supported research 502
  • Politics of hESC research in the US 503
  • Public opinion in the US about hESC research 505
  • Human stem cell cloning in the US 506
  • Stem cell guidelines of various US institutions 507
  • Ethics of transplanting human NSCs into the brains of nonhuman primates 507
  • ESC lines available worldwide 508
  • ESC policies around the world 509
  • Countries with no defined policies on hESC research 509
  • Australia 510
  • Canada 510
  • China 511
  • Denmark 512
  • France 512
  • Germany 512
  • India 514
  • Ireland 515
  • Israel 515
  • Italy 515
  • Japan 516
  • The Netherlands 516
  • Saudi Arabia 517
  • Singapore 517
  • South Africa 517
  • South Korea 518
  • Spain 518
  • Sweden 518
  • Switzerland 519
  • United Kingdom 519
  • UK StemCellBank 520
  • European Union 521
  • EU guidelines for stem cell research 521
  • European stem cell bank 523
  • EMBO's recommendations for stem cell research 523
  • Public opinion in Europe about hESC research 524
  • United Nations, cloning and nuclear transfer 525
  • The Embryo Project for information on ESC research 525
  • Concluding remarks about ethics of ESC research 525
  • Ethical issues concerning umbilical cord blood 525
  • Legal issues associated with stem cells 526
  • Stem cell patents 526
  • Stem cell patents in the United States 526
  • Current status of Thomson patents at WARF 527
  • Stem cell patents in the European Union 527
  • Cell therapy tourism 528

9. Safety and Regulatory Aspects of Cell Therapy 530

  • Introduction 530
  • Safety issues of cell therapy 530
  • Immune-mediated reactions to transpanted stem cells 530
  • Human virus infections associated with stem cell transplantation 531
  • Herpes simplex virus type 1 531
  • Cytomegalovirus 531
  • Opportunistic infections among hematopoietic stem cell transplant recipients 531
  • Cord colitis syndrome 531
  • Carcinogenic potential of stem cells and its prevention 532
  • FDA safety regulations for cell and tissue products 532
  • FDA Guidance on license applications for umbilical cord blood products 533
  • Regulation of cord blood banks in the US 533
  • Regulatory issues for biotechnology-derived drugs 533
  • Regulation of cell selection devices for PBSCs at point of care 534
  • FDA rules for human cells and tissues 535
  • FDA regulation of fetal cellular or tissue products 535
  • FDA and ESC lines 536
  • FDA and clinical trials using hESCs 536
  • Cell and gene therapy INDs placed on hold by the FDA 537
  • Regulatory issues for genetically engineered cell transplants 537
  • FDA guidelines for human tissue transplantation 538
  • FDA considers cultured stem cells for therapy as drugs 538
  • Xenotransplantation 538
  • Clinical Protocol Review and Oversight 538
  • Informed consent and patient education 539
  • Xenotransplantation product sources 539
  • FDA guidelines for xenografts 539
  • Regulatory challenges for the clinical use of cell products 541
  • Regulations relevant to cell therapy in the European Union 541
  • Regulations about use of stem cells in the EU 543
  • Guidelines for cell therapy in the UK 543
  • NIH and stem cells 544
  • hESC lines approved under the new NIH guidelines 544
  • Clinical trials in cell therapy 544

Tables

  • Table 1-1: Landmarks in the history of cell therapy 28
  • Table 1-2: Examples of cells involved in various diseases 33
  • Table 2-1: Types of human cells used in cell therapy 38
  • Table 2-2: A selection of companies providing cell culture media 42
  • Table 2-3: A sampling of companies supplying cell sorters 48
  • Table 2-4: Companies involved in cell-based drug discovery 56
  • Table 2-5: Methods of delivery of cells for therapeutic purposes 58
  • Table 2-6: Therapeutic applications of encapsulated cells 63
  • Table 2-7: Companies working on encapsulated cell technology 65
  • Table 2-8: Molecular imaging methods for tracking cells in vivo 71
  • Table 3-1: Companies involved in cord blood banking as a source of stem cells 108
  • Table 3-2: Banks of patient-specific iPSC lines 115
  • Table 3-3: Companies providing iPSCs 116
  • Table 3-4: Sources of adult human stem cells 120
  • Table 3-5: Comparison of human stem cells according to derivation 130
  • Table 3-6: Enhancing engraftment, mobilization and expansion of stem cells 150
  • Table 3-7: Applications of stem cells 168
  • Table 3-8: Advantages and limitations of methods for optimizing MSCs 179
  • Table 3-9: Pharmaceutical manipulation of stem cells 185
  • Table 3-10: Growth factors with positive effects on stem cells and applications 187
  • Table 3-11: Examples of drugs that induce granulocytopenia at stem cell level 198
  • Table 3-12: Academic institutes involved in stem cell research 205
  • Table 3-13: Companies involved in stem cell technologies 207
  • Table 4-1: Therapeutic applications of regulatory T cells (T-regs) 223
  • Table 4-2: Various tissue/cell therapy approaches to the treatment of type 1 diabetes 230
  • Table 4-3: Companies involved in cell therapy for insulin-dependent diabetes 246
  • Table 4-4: Major pulmonary disorders potentially treatable by stem cell manipulation 264
  • Table 4-5: Cell-based repair of knee cartilage damage 281
  • Table 4-6: Intraoperative cell therapy 307
  • Table 5-1: Classification of various types of cell therapy for cardiovascular disorders 311
  • Table 5-2: Clinical trials of cell therapy in cardiovascular disease 349
  • Table 6-1: Cell therapy technologies used for cancer 356
  • Table 6-2: Companies involved in developing cell-based therapies for cancer 392
  • Table 7-1: Experimental use of immortalized cells for CNS disorders 413
  • Table 7-2: Combination of stem cells and HBO in models of neurological disorders 419
  • Table 7-3: Methods for delivering cell therapies in CNS disorders 420
  • Table 7-4: Neurological disorders amenable to cell therapy 425
  • Table 7-5: Types of cell used for investigative treatment of Parkinson's disease 430
  • Table 7-6: Status of cell therapies for Parkinson's disease 431
  • Table 7-7: Role of cell therapy in management of stroke according to stage 456
  • Table 7-8: Clinical trials of cell therapy for stroke: completed, ongoing and pending 456
  • Table 7-9: Clinical trials with cell-based therapies in neurological disorders (excluding stroke) 496
  • Table 8-1: Listed numbers of ESC lines around the world 508
  • Table 8-2: Stem cell policies around the world 509
  • Table 8-3: European public attitudes about research involving human stem cells 524
  • Table 9-1: Possible adverse reactions and safety issues of cell therapy 530

Figures

  • Figure 1-1: Interrelationships of cell therapy to other technologies 30
  • Figure 1-2: Interrelationships of gene, cell and protein therapies 32
  • Figure 3-1: A simplified biological scheme of embryonic stem Cells 79
  • Figure 3-2: Steps of iPS cell production 112
  • Figure 3-3: hESC-derived by somatic cell nuclear transfer 147
  • Figure 3-4: Flow chart of development of stem cells with potential bottlenecks 213
  • Figure 4-1: Reprograming ESCs/iPSCs cells to Β-cells for type 1 diabetes 242
  • Figure 5-1: Ex vivo vs in vivo approaches to regeneration of the heart 311
  • Figure 5-2: hESC-derived cardiomyocytes from laboratory to bedside 324
  • Figure 5-3: Steps in growing a new heart in vitro for transplantation 346
  • Figure 6-1: A scheme of generation and administration of tumor antigen-pulsed dendritic cells 366
  • Figure 6-2: Stem cell transplantation techniques 374
  • Figure 7-1: Stem cells that can give rise to neurons 404
  • Figure 7-2: Approaches to stem cell therapy in stroke 452

Part II

10. Markets and Future Prospects for Cell Therapy 6

  • Introduction 6
  • Methods for estimation of cell therapy markets 6
  • Potential markets for cell therapy 7
  • Markets according to technologies 7
  • Stem cell transplants 7
  • Supporting cell technologies 8
  • Blood transfusion market 8
  • Cord blood collection and storage 8
  • Cell therapy and related technologies 8
  • Cell therapy markets according to therapeutic area 8
  • Bone and joint disorders 9
  • Cancer 9
  • Cardiovascular disorders 10
  • Diabetes mellitus 10
  • Liver disorders 11
  • Neurological disorders 11
  • Retinal degenerative diseases market 12
  • Skin and wound care 12
  • Urinary incontinence 12
  • Reconstruction of teeth by stem cell implants 12
  • Market size according to geographical areas 13
  • Unmet market needs in cell therapy 14
  • Drivers of growth of cell therapy markets 14
  • Role of stem cells in regenerative medicine 14
  • Role of cells in markets for artificial organs 15
  • Increase of R&D expense on cell therapy 15
  • Increased used of cell-based drug discovery 15
  • Impact of emerging healthcare trends on cell therapy markets 15
  • Markets for cell therapy tourism 15
  • Involvement of pharmaceutical companies in cell therapy 16
  • Future prospects of cell therapy 16
  • Embryonic stem cell research around the world 16
  • Consortia for ESC research in Europe 17
  • EuroStemCell 17
  • FunGenES 18
  • ESTOOLS 18
  • UK National Stem Cell Network 19
  • Ethical concerns about commercialization of embryonic stem cells 20
  • Education of the physicians 20
  • Public education 20
  • NIH support of stem cell research 20
  • Funding of stem cell research from non-federal sources 21
  • Prospects of venture capital support for stem cell companies 22
  • Cell therapy in the developing countries 23
  • Guidelines for stem cell therapies 24
  • Business strategies 24
  • Formation of networks 25
  • Market potential of autologous vs allogeneic cells 25
  • Future market potential of adult vs embryonic stem cells 26

11. Companies Involved in Cell Therapy 28

  • Introduction 28
  • Profiles of selected companies 30
  • Collaborations 349

12. Academic Institutions 360

  • Introduction 360
  • Stem cell center 360
  • Profiles of institutions 361
  • Collaborations 450

13. References 454

Tables

  • Table 10-1: Market size according to cell therapy and related technologies 2013-2023 7
  • Table 10-2: Market size according to therapeutic areas for cell therapy in 2013-2023 9
  • Table 10-3: Cell therapy markets for cardiovascular disorders in 2013-2023 10
  • Table 10-4: Values of cell therapies for neurological disorders in 2013-2023 11
  • Table 10-5: Total cell therapy market in 2013-2023 according to geographical areas 13
  • Table 10-6: Cord blood market according to geographical areas 2013-2023 13
  • Table 10-7: Stem cells transplant market according to geographical areas 2013-2023 13
  • Table 10-8: SWOT Autologous cells vs allogeneic cells 25
  • Table 11-1: Publicly traded cell therapy companies 28
  • Table 11-2: Selected collaborations of cell therapy companies 349
  • Table 12-1: Therapeutic uses of stem cells 368
  • Table 12-2: Commercial collaborations of US academic institutes relevant to stem cells 450

Figures

  • Figure 10-1: Unmet needs in cell therapy 14
Back to Top