Stem cell therapy : practical considerations

Stem cell therapy is a fast-growing field of medicine with remarkable prospects in a broad spectrum of diseases. Stem Cell Therapy: Practical Considerations addresses the biological properties of stem cells, mechanisms of action; as well as actual therapeutic decisions such as cell type, source, dose, manipulation, and route of injection. After discussing all this data, the book will illustrate how to travel through the idea from abstract question to laboratory experiment, animal experiment and then on to design a clinical trial throughout all its phases. Written for scientists and postgraduate students in the field of stem cell research and therapy. The authors will cover practical therapeutic issues they have long experienced in the field. Front Cover Stem Cell Therapy Copyright Page Dedication Contents I. Stem cells: basic biology 1 Introduction 1.1 Establishing the concept of stem cells Further reading 2 Anatomy and Histology 2.1 Blood supply 2.2 Niche 2.3 Hemopoietic stem cell niches 2.4 Differences between osteoblastic and vascular niches 2.5 Components of the hemopoietic stem cell niche 2.6 Mesenchymal stem cell niche 2.6.1 Bone marrow mesenchymal stem cell niche 2.7 Mesenchymal stem niche in adipose tissue 2.7.1 Epidermal stem cell niche 2.7.2 Intestinal epithelial niche 2.8 Niche functions 2.9 Regulation of niche function Further reading 3 Stem cells: definition, biological types, classifications, and properties 3.1 Definition 3.2 Classification 3.3 Properties 3.3.1 Potency 3.3.1.1 Totipotent stem cells 3.3.1.2 Pluripotent stem cells 3.3.1.3 Molecular determinants of pluripotency 3.3.1.4 Cell cycle profile of pluripotency 3.3.1.5 Multipotent stem cells 3.3.1.6 Oligopotent stem cells 3.3.1.7 Bipotent stem cells 3.3.1.8 Unipotent stem cells 3.3.2 Self-renewal 3.3.2.1 Regulation of self-renewal 3.3.3 Stem cell plasticity 3.3.4 Evidence of stem cell transdifferentiation 3.3.5 Theories of transdifferentiation 3.3.5.1 Requirements for proof of transdifferentiation 3.3.5.2 Factors affecting frequency of transdifferentiation 3.3.5.3 Induction of transdifferentiation 3.3.5.4 Evaluation of transdifferentiation 3.4 Differentiation 3.5 Homing and engraftment 3.5.1 Definition 3.5.2 Mechanism of homing 3.5.3 Enhanced and directed homing 3.5.4 Stem cell trafficking 3.5.5 Mechanism of stem cell trafficking 3.5.6 Role of stem cell trafficking in regeneration Further reading II. Stem cell induced regeneration: principles and applications 4 Mechanisms of stem cell–related regeneration 4.1 Regulation of tissue regeneration 4.2 Overview of the mechanism of regeneration 4.2.1 Transdifferentiation 4.2.2 Contribution to tissue regeneration 4.2.3 Variation in transdifferentiation potential 4.2.4 Molecular mechanisms of transdifferentiation 4.3 Signaling pathways involved in stem cell transdifferentiation Mogrify algorithm 4.4 Activation of endogenous repair system 4.5 Induction of angiogenesis 4.5.1 Variability in angiogenic potential of mesenchymal stem cells 4.6 Secretory function 4.6.1 Microvesicles and exosomes 4.6.2 Paracrine action 4.7 Mitochondrial transfer 4.7.1 Inducers of transfer 4.7.2 Mechanisms 4.7.3 Effects 4.7.4 Variability in mitochondrial transfer according to mesenchymal stem cell source 4.8 Microenvironment modulation 4.9 Conclusion Further reading 5 Sources of stem cells for regenerative purposes 5.1 Characteristics of the ideal source of stem cells 5.2 Sources of mesenchymal stem cells 5.3 Skin mesenchymal stem cells 5.4 Periodontal ligament stem cells 5.4.1 Sources of hemopoietic stem cells 5.5 Cord blood 5.5.1 Sources of endothelial cells 5.6 Tissue-specific stem cells Further reading 6 Basic concepts in stem cell therapy: stem cell therapy strategy development 6.1 Introduction 6.2 What is the basic defect? 6.2.1 Cellular defects 6.2.2 Structural defects 6.3 Which cell lineage is the best for repair? Choosing optimum cell lineage 6.4 What is the best source for a cell type? Choosing the optimum cell source 6.4.1 Hemopoietic stem cells 6.4.2 Mesenchymal stem cells 6.5 What is the optimum laboratory protocol? 6.6 Choosing the optimum route of injection 6.7 Factors affecting homing of stem cells 6.7.1 Methods to improve stem cell homing 6.7.2 Mesenchymal stem cell homing 6.8 Optimal timing for cell therapy 6.9 Optimum number of cells for injection 6.10 Choosing the method of evaluation Further reading III. Guidelines for stem cell therapy 7 Stem Cell Therapy: Laboratory guidelines 7.1 Introduction 7.1.1 Regulatory bodies 7.1.1.1 Stem cell therapy types in regard to manipulation 7.2 Laboratory guidelines 7.2.1 Structural facilities 7.2.1.1 Good tissue practice 7.2.1.1.1 Good tissue practice environmental control 7.2.1.2 Good manufacturing practice 7.2.1.2.1 Facilities 7.2.1.2.2 Equipment 7.2.1.2.3 Basic equipment for stem cell laboratory are 7.2.1.2.4 Supplies and reagents 7.2.1.2.5 Processing and process control 7.2.2 Personnel qualifications and job description 7.2.2.1 Administrative team 7.2.2.2 Ethics team 7.2.2.3 Clinical evaluation team 7.2.2.4 Stem cell collection team 7.2.2.5 Stem cell handling team (laboratory) 7.2.2.6 Clinical followup team 7.3 Quality control team Further reading 8 Protocol guidelines for clinical decisions in stem cell therapy 8.1 Introduction 8.1.1 Timing of intervention 8.1.2 Stem cell injection 8.1.2.1 Route of injection 8.1.3 Frequency of injection 8.1.3.1 Methods of evaluation 8.1.3.1.1 Patient 8.1.3.1.2 Cells Reference Further reading 9 Protocol guidelines: laboratory decisions in stem cell therapy 9.1 Introduction 9.2 Choosing the cell purification level 9.3 Choice of purification strategy 9.4 Choice of stem cell differentiation status 9.5 Choice of cell dose 9.6 Choice of tracking method 9.6.1 Methods of in vivo cell tracking 9.6.1.1 Experimental 9.6.1.2 Methods of in vivo tracking in humans 10 Phases of translational stem cell research 10.1 Introduction 10.2 Laboratory experiments 10.3 Preclinical, experimental 10.3.1 Value of animal experiments 10.3.1.1 Animal models 10.3.1.2 Species selection 10.3.1.3 Strain selection 10.3.1.4 Methods of inducing animal models 10.3.2 Small versus large animals 10.3.3 Challenges in animal experiments 10.3.4 Ethical considerations 10.4 Clinical trials Further reading 11 Ethical guidelines of stem cell therapy 11.1 Introduction 11.1.1 Ethical guidelines for the use of embryonic cells 11.1.2 Ethical concerns 11.1.3 Ethical guidelines for preclinical studies 11.1.4 Principles of ethical guidelines of clinical translation Further reading 12 Stem cell therapy: practical examples 12.1 Neuroregeneration 12.1.1 In vitro experiments 12.2 Experimental animal study 12.2.1 Induction of animal model 12.2.2 Stem cell therapy 12.2.3 Followup 12.3 Results 12.3.1 Clinical translational study 12.4 Results of clinical translational study 12.5 Replacement of defective protein 12.5.1 Epidermolysis bullosa 12.6 Results 12.7 Multifactorial defects 12.7.1 Results 12.7.1.1 In vitro experiments 12.7.1.2 Clinical results 12.8 Conclusion Further reading Appendix A A.1 Standard operating procedures for stem cell therapy procedures A.1.1 Collection A.1.1.1 Collection of peripheral blood hemopoietic stem cells A.1.1.2 Collection of bone marrow hemopoietic stem cells A.1.1.3 Cord blood stem cell collection A.1.1.4 Collection of stem cells from adipose tissue A.1.2 Isolation A.1.2.1 Mononuclear cell separation by density gradient centrifugation A.1.2.2 Mesenchymal Stem Cell Isolation from Wharton Jelly A.1.3 Mesenchymal stem cell culture A.1.3.1 Identification of mesenchymal stem cells A.1.4 Differentiation A.1.4.1 Plating cells for differentiation A.1.4.2 Evaluation of differentiation A.1.5 Coating of flasks A.1.6 Labeling Index Back Cover