Human iPSC-derived Disease Models for Drug Discovery (Handbook of Experimental Pharmacology, 281)

Preface
Contents
Part I: iPSC Production for Pharmaceutical Research
	Human iPS Cells for Clinical Applications and Cellular Products
		1 Pluripotency and Stem Cell Culture
		2 Reprogramming: Reversing Developmental Time
			2.1 Reprogramming Human Cells
			2.2 Safety of iPSCs
		3 Manufacturing Safe Therapeutics from iPSCs
		4 Transferring to GMP Grade
			4.1 Freedom to Operate
			4.2 iPSC Quality Control
				4.2.1 Mutations
				4.2.2 Gene Editing
				4.2.3 Differentiation Capacity
		5 Cellular Products
			5.1 Introduction
			5.2 Retinal and Corneal Cells from iPSCs
			5.3 Neural Cells for Parkinson´s Disease and Spinal Cord Injury
			5.4 Heart Failure
			5.5 Transfusion Products
			5.6 Mesenchymal Stromal Cells and Cartilage
			5.7 Targeting Cancer Using iPSC-Derived Therapies
		6 Conclusion
		References
	3D Bioprinting of Induced Pluripotent Stem Cells and Disease Modeling
		1 Introduction
		2 Overview of 3D Printing
		3 Bioinks for Bioprinting
		4 Bioinks for iPSC Bioprinting
		5 3D Bioprinting of iPSCs
		6 Inkjet Bioprinting
		7 Microextrusion-Based Bioprinting
		8 Stereolithography (SLA)-Based Bioprinting
		9 Laser-Assisted Bioprinting
		10 iPSC-Based Bioprinting for Disease Modeling
		11 Bioprinting of iPSC-Derived Cells for Cardiac Disease Models
		12 Bioprinted iPSC-Derived Neural Physiological and Disease Models
		13 Outlook
		References
Part II: CNS iPSC and Organoids
	iPSCs-Derived Neurons and Brain Organoids from Patients
		1 Introduction of iPSCs
		2 iPSCs-Derived Neurons
		3 Application of iPSCs-Derived Neurons for Disease Modeling
		4 iPSCs-Derived Brain Organoids
		5 Application of iPSCs-Derived Brain Organoids for Disease Modeling
		6 Applications for Transplantation
		7 Conclusion
		References
	Retinal Ganglion Cells in a Dish: Current Strategies and Recommended Best Practices for Effective In Vitro Modeling of Develop...
		1 Introduction
		2 Established Approaches for the Directed Differentiation of Human RGCs
		3 Essential Characteristics for hPSC-RGCs
		4 Modeling RGC Neurodegeneration with hPSCs and the Necessity for Proper Controls
		5 Future Directions for Advancing hPSC-RGC Technologies
		6 Concluding Remarks
		References
	Applications of Induced Pluripotent Stem Cell-Derived Glia in Brain Disease Research and Treatment
		1 Introduction
			1.1 Astrocytes
			1.2 Oligodendrocytes
			1.3 Microglia
		2 Glia Involvement in Brain Diseases
			2.1 Brain Diseases Involving Astrocytes
				2.1.1 Alzheimer´s Disease (AD)
				2.1.2 Parkinson´s Disease (PD)
				2.1.3 Huntington´s Disease (HD)
				2.1.4 Traumatic Brain Injury
				2.1.5 Ischemia/Stroke
			2.2 Brain Diseases Involving Microglia
				2.2.1 Alzheimer´s Disease (AD)
				2.2.2 Parkinson´s Disease (PD)
				2.2.3 Ischemia/Stroke
			2.3 Brain Diseases Involving Oligodendrocytes
				2.3.1 Krabbe Disease
				2.3.2 Multiple Sclerosis (MS)
				2.3.3 Alzheimer´s Disease (AD)
				2.3.4 Ischemia/Stroke
		3 Generation of Induced Pluripotent Stem Cell (iPSC)-Derived Glia
			3.1 Generation of iPSC-Derived Astrocytes
			3.2 Generation of iPSC-Derived Microglia
			3.3 Generation of iPSC-Derived Oligodendrocytes
		4 Research Models of Pluripotent Stem Cell-Derived Glia to Define the Role of Glial Pathology in Human Disease
			4.1 Pathophysiological Neuroglial Interaction Models in 2D Cell Cultures
				4.1.1 Alzheimer´s Disease (AD)
				4.1.2 Parkinson´s Disease (PD)
				4.1.3 Huntington´s Disease (HD)
			4.2 3D Brain Organoids from iPSC-Derived Neurons and Glia
				4.2.1 Alzheimer´s Disease
				4.2.2 Parkinson´s Disease
				4.2.3 Limitations and Improvements
			4.3 Chimeric Mice from iPSC-Derived Glia
			4.4 Functional Decoding of iPSC-Derived Astrocytes Combined with Ca2+ Imaging at Multiple Levels
		5 Potential Methods of Treatment Using Pluripotent Stem Cell-Derived Glia
			5.1 Treatment by iPSC-Derived Astrocytes
				5.1.1 Alzheimer´s Disease (AD)
				5.1.2 Parkinson´s Disease (PD)
				5.1.3 Huntington´s Disease (HD)
				5.1.4 Traumatic Brain Injury (TBI)
				5.1.5 Ischemia/Stroke
				5.1.6 Integration of Transplanted Astrocytes and Behavioral Improvements
			5.2 Treatment by iPSC-Derived Microglia
			5.3 Treatment by iPSC-Derived Oligodendrocytes
				5.3.1 Pediatric Disease Targets of GPC-Based Therapy
				5.3.2 Adult Disease Targets of GPC-Based Treatment
		6 Conclusion
		References
	Human-Induced Pluripotent Stem Cell-Based Model of the Blood-Brain at 10 Years: A Retrospective on Past and Current Disease Mo...
		1 Introduction
		2 Modeling Diseases at the BBB Using Induced Pluripotent Stem Cells
			2.1 Adrenoleukodystrophy
			2.2 Allan-Herndon-Dudley Syndrome (AHDS)
			2.3 Alzheimer´s Disease
			2.4 Amyotrophic Lateral Sclerosis (ALS)
			2.5 Cerebral Hypoxia/Ischemia
			2.6 COVID-19
			2.7 GLUT1 Deficiency Syndrome
			2.8 Huntington´s Disease
			2.9 Neural Ceroid Lipofuscinosis
			2.10 Pathogen-Host Interactions
		3 Limitations and Challenges of iPSC-Based Models of the BBB in Disease Modeling
		4 Concluding Remarks
		References
	Human Retinal Organoids in Therapeutic Discovery: A Review of Applications
		1 Introduction
		2 Research that Paved the Way for RO Technology
		3 Methods of Induction of Human ROs
			3.1 The SFEBq (3D) Method
			3.2 The 3D-2D-3D Culture Method
			3.3 Summary
		4 Human ROs Are Used Extensively to Study Disease Mechanisms
		5 Human RO-Derived Cells Are a Valuable Resource for Biobanking for Regenerative Medicine
			5.1 Dissociated Photoreceptor Transplantation
			5.2 Dissociated RGC Transplantation
			5.3 RPE Transplantation
			5.4 Retinal Sheet Transplantation
			5.5 Challenges of Cell Replacement Therapy
		6 Human RO-Derived Cells Are Widely Used for Disease Modeling
		7 Use of Human ROs for Therapeutic Development
			7.1 Drug Toxicity and Efficacy Screening
			7.2 Gene Therapy and Genetic Editing
		8 ROs Can Be Integrated with Other Technologies to Broaden the Range of Investigation
		9 Challenges of Current RO Technology
			9.1 Variation Limits Reliability and Producibility
			9.2 Cryopreservation Compromises the Morphology and Cellularity of ROs
			9.3 Degeneration of Retinal Cells with Prolonged Culture
			9.4 The Absence of Vascular and Glial Cells Limits the Use of ROs
		10 Outlook and Future Directions
		References
Part III: iPSC-Derived Nociceptive Neurons
	Using Human iPSC-Derived Peripheral Nervous System Disease Models for Drug Discovery
		1 Introduction
		2 What Is Human iPSC
			2.1 Overview of Human IPSC
			2.2 Application Prospects of Human IPSC
		3 What Is Peripheral Neuropathy
			3.1 Overview of Peripheral Nerve Diseases
			3.2 Traditional Treatment of Peripheral Nerve Diseases
			3.3 Feasibility of IPSC-Derived Models for Peripheral Nerve Diseases Treatment
		4 Application of Disease Models in Peripheral Neuropathy
			4.1 Limitations of Traditional Disease Models
			4.2 Advantages of Human iPSC-Derived Peripheral Disease Models
			4.3 Basic Steps in IPSC-Derived Disease Modeling
			4.4 Classification of IPSC-Derived Disease Modeling
		5 Application of Different Human IPSC-Derived Models for Peripheral Nerve Diseases in Drug Discovery
			5.1 Neuromuscular Junction Model
			5.2 Neural Crest Model
			5.3 Various IPSC-Derived Neuronal Cell Subtypes
				5.3.1 Neural Mesodermal Model
		6 Conclusion
		References
Part IV: Non-Neuronal Specialized Cell Types
	Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy
		1 Introduction
		2 Different Drug Screening Platforms and the Emergence of Human iPSCs
			2.1 Animal Models
			2.2 In Vitro Models
			2.3 Adult Human Cardiomyocytes
		3 Human iPSC-CMs and Their Subtypes
			3.1 Generation of Ventricular-Like Cardiomyocytes from iPSCs for Cell Therapy and Drug Discovery
			3.2 Generation of Atrial-Like Cardiomyocytes from iPSCs for Cell Therapy and Drug Discovery
			3.3 Generation of Nodal-Like Cardiomyocytes from iPSCs and Use in Cell Therapy
		4 Conclusions
		References
	Cardiac Disease Modeling with Engineered Heart Tissue
		1 Functional and Structural Basis of Beating Heart
			1.1 Function of Heart
			1.2 Cellular and Structural Composition of Heart
		2 History and Different Strategies for Building the Engineered Heart Tissue
			2.1 Key Questions in Engineered Heart Tissue Building
			2.2 Strategies for Constructing EHT
		3 Cardiac Disease Modeling Using EHT
			3.1 Cardiac Organoid Model
			3.2 Cardiac Thin-Film Model
			3.3 Microbundle Model
		4 Concluding Remarks
		References
	iPSC-Derived Corneal Endothelial Cells
		1 Introduction
		2 Corneal Endothelium
			2.1 Development of Corneal Endothelium
			2.2 Corneal Endothelial Physiology
			2.3 Treatment of Corneal Endothelial Decompensation
		3 Generation of iPSC-Derived Corneal Endothelial Cells (CECs)
			3.1 Strategies of iPSC-Derived CECs
			3.2 Molecular Profiling and Characteristics
		4 iPSC-Based Models of Corneal Endothelial Dysfunction
		5 Applications of iPSC-Derived CECs for Corneal Endothelial Dysfunction
			5.1 Tissue Engineering Corneal Endothelium
			5.2 Therapeutic Function
			5.3 Therapeutic Mechanism
		6 Future Applications and Challenges
		7 Summary
		References
	iPSCs-Based Therapy for Trabecular Meshwork
		1 Introduction
		2 Trabecular Meshwork
			2.1 Trabecular Meshwork Physiology
			2.2 Trabecular Meshwork Pathology
		3 Novel Treatments for the Damaged TM
		4 In Vitro Models for TM
			4.1 Conventional Models
				4.1.1 Primary TM Cells
				4.1.2 Immortalized Lines of TM Cells
			4.2 Induced Pluripotent Stem Cell (iPSC)-Based Models
			4.3 3D Models
			4.4 Bioreactor
			4.5 Glaucoma Models
		5 iPSC-Based Therapy for the Damaged TM
			5.1 TM Regeneration in Mouse and Human
				5.1.1 Tg-MYOCY437H Mice
				5.1.2 sGCα1-Deficient Mice
				5.1.3 TM Regeneration in Human Eyes
			5.2 Mechanism of TM Regeneration
			5.3 Challenges for Clinical Translation
		6 Conclusion
		References
	Harnessing Human Pluripotent Stem Cell-Derived Pancreatic In Vitro Models for High-Throughput Toxicity Testing and Diabetes Dr...
		1 Introduction
		2 Current Available Pancreatic Cell Models for Studying Diabetes
			2.1 Human and Animal Cadaveric Islets
			2.2 Rodent Insulinoma Lines
			2.3 Human Insulinoma Lines
			2.4 hiPSC-Derived Pancreatic β-Like Cell Models
		3 High-Throughput Screening (HTS) Platforms
			3.1 β-Cell Survival
			3.2 β-Cell Proliferation
			3.3 Insulin Expression/Release
		4 Conclusion
		References