Stem Cells in Veterinary Science

Preface
Contents
Editors and Contributors
Part I: Overview and Introduction
	1: Overview of Stem Cells and Their Applications in Veterinary Medicine
		1.1 History of Stem Cells
		1.2 Types of Stem Cells
		1.3 Stem Cells of Veterinary Importance
		1.4 Adult Stem Cells
		1.5 Mechanisms of Stem Cell Actions
		1.6 Clinical Applications of Stem Cells in Regenerative Veterinary Medicine
		1.7 Conclusions
		References
	2: Introduction to Mammary Gland and Its Cell Types
		2.1 Prenatal Development of the Mammary Gland
		2.2 Postnatal Development of the Mammary Gland
			2.2.1 Early Development
			2.2.2 Prepubertal Development
		2.3 Mammary Growth During Pregnancy
		2.4 Mammary Growth During Lactation
		2.5 Post-lactational Mammary Gland Involution
		2.6 Gross Morphology of Ruminant Mammary Gland
		2.7 Histomorphology of Mammary Gland
		2.8 Types of Cells in the Mammary Gland
		2.9 Mammary Epithelial Cell (MEC)
		2.10 Myoepithelial Cells
		2.11 Adipocytes
		2.12 Mammary Stem/Progenitor Cell
		References
	3: Mammary Stem Cells: How Much Do We Know?
		3.1 Introduction
		3.2 Discovery, Isolation, and Characterization of MaSCs
		3.3 Single MaSC Can Form an Entire Mammary Gland
		3.4 Endocrine Regulation of MaSCs
		3.5 Significance and Relevance to Dairy Animals and Humans Health
		3.6 Conclusion
		References
	4: Methods of Identification and Characterization of Stem Cells
		4.1 Introduction
		4.2 Identification and Isolation of Stem Cells
			4.2.1 Embryonic Stem Cells
			4.2.2 Adult Stem Cells
		4.3 Characterization of Stem Cells
		References
	5: Potential of Stem Cell Therapy to Combat Mastitis in Dairy Animals
		5.1 Mastitis
		5.2 Etiology of Mastitis
		5.3 Mammary Gland
		5.4 Structure
		5.5 Effect of Mastitis on Mammary Gland Structure
		5.6 Stem Cell Biology
		5.7 How Does Stem Cell Technology Work to Combat?
		5.8 Bovine Mammary Stem/Progenitor Cells
		5.9 Caprine Mammary Stem Cells
		5.10 Murine Mammary Stem Cells
		5.11 Mesenchymal Stem Cells (MSCs)
		5.12 Adipose Stem Cells
		5.13 Limitations
		5.14 Conclusion and Future Needs
		References
Part II: Stem Cells and Veterinary Research
	6: Fatty Liver Disease and Utility of Stem Cells in Developing the Disease Model
		6.1 Histology of Liver
		6.2 Pathology of the Liver and Altered Histology
		6.3 Characteristics of the Transition Period
		6.4 Homoerotic Shifts in Glucose Partitioning Support Lactation
		6.5 Altered Glucose Partitioning Promotes Mobilization of Energetic Reserves in Adipose Tissue
		6.6 Mobilization of TAG from Adipose Tissue in the Periparturient Period
		6.7 Limited Protein Intake Results in Impaired VLDL Secretion and Mitochondrial Dysfunction
		6.8 The Immune System is Impaired in the Transition Period Because of Inadequate Glucose and Elevated NEFA
		6.9 Impaired Hepatic Function Results in Impaired Gluconeogenesis
		6.10 Early Lactation Requires Coordinated Shifts in Lipid and Glucose Metabolism
		6.11 MCJ and Mitochondrial Function: Decreased Triacylglycerol Accumulation
		6.12 Bovine FLD as a Model of NASH and NAFLD
		6.13 In Vitro Models of NAFLD
		6.14 Stem Cells as an Alternative Source of Individual-specific Hepatic Cells
		6.15 Other Possible Hepatic Cell Culture Models of Bovine FLD
		6.16 Conclusions
		References
	7: Mammary Epithelial Cells: A Potential Cellular Model to Understand the Impact of Heat Stress on Mammary Gland and Milk Prod...
		7.1 Introduction
		7.2 Economic Consequences of Heat Stress on Livestock Production
		7.3 Heat Stress and Milk Yield
		7.4 Impact of Heat Stress on Mammary Gland of Dairy Animals
		7.5 Mammary Epithelial Cells as a Cellular Model to Understand the Heat Stress Response
		7.6 Conclusion
		References
	8: Milk and Milk-Derived Stem Cells
		8.1 Milk Composition
		8.2 Milk Fat
		8.3 Milk Protein
		8.4 Minerals, Antioxidants, and Vitamins in Milk
		8.5 Immunoglobulins in Milk
		8.6 Milk Exosomes
		8.7 Milk Probiotics
		8.8 Milk-Derived Stem Cells
		8.9 Therapeutic Applications of Milk-Derived Stem Cells
		References
	9: Cryopreservation of Testicular Stem Cells and Its Application in Veterinary Science
		9.1 Introduction
		9.2 Methods of Cryopreservation of Testicular Stem Cells
		9.3 Freezing of Testicular Stem Cells
			Box 9.1 A Suggested Protocol for Slow Freezing of Testicular Stem Cells in Mechanical Freezer
		9.4 Vitrification of Testicular Stem Cells
			Box 9.2 A Suggested Protocol for Vitrification of Testicular Stem Cells by SSV
			9.4.1 Cryocontainers for Vitrification
		9.5 Cryoprotective agents (CPA) for Freezing and Vitrification
		9.6 CPA Toxicity and Strategies for Its Amelioration
		9.7 Cryoinjury and Strategies for Its Amelioration
		9.8 Assessing the Viability of Cryopreserved Testicular Stem Cells
		9.9 Biochemical Assays
		9.10 Molecular Methods
		9.11 Transplantation Assays
		9.12 In Vitro Spermatogenesis
		9.13 Application of Testicular Stem Cell Cryopreservation
		9.14 Fertility Restoration in Males with Pre- and Post-meiotic Barriers to Spermatogenesis
		9.15 Male Fertility in Ageing
		9.16 Posthumous Reproduction
		9.17 Fertility Preservation and Restoration in Pre-pubertals with Oncological Conditions
		9.18 Fertility Preservation and Restoration in Non-oncological Diseases
		9.19 Animal Transgenesis and Genome Editing
		9.20 Banking for Preservation and International Movement of Animal Genetic Resources
		9.21 Challenges and Future Perspectives
		9.22 Conclusions
		References
	10: Testicular Stem Cell Niche
		10.1 Introduction
		10.2 Histoarchitecture of Testis
			10.2.1 Stroma
				10.2.1.1 Testicular Coverings
				10.2.1.2 Septae and Medistinum Testis
			10.2.2 Parenchyma
				10.2.2.1 Seminiferous Tubules
					Types of Cells Within Seminiferous Tubules
				10.2.2.2 Interstitial Tissue
				10.2.2.3 Rete Testis
		10.3 TSC Niche
			10.3.1 Sertoli Cells
			10.3.2 Basement Membrane of Seminiferous Tubules
			10.3.3 PM Cells
			10.3.4 Leydig Cells
			10.3.5 Blood Vessels
			10.3.6 Macrophages
		10.4 Ontogeny of TSC Niche
		10.5 Factors Influencing TSC Niche
			10.5.1 Intrinsic Factors
				10.5.1.1 Taf4b
				10.5.1.2 Plzf
				10.5.1.3 Chd1l
			10.5.2 Extrinsic Factors
				10.5.2.1 ERM/Etv5 Transcription Factor
				10.5.2.2 GDNF
					Ras Signalling Pathway
					Src Signalling Pathway
					FGFR2 Signalling Pathway
					B Cell CLL/Lymphoma 6, Member B (Bcl6b)
				10.5.2.3 Fibroblast Growth Factor 2 (FGF2)
				10.5.2.4 Colony-Stimulating Factor 1 (CSF-1)
			10.5.3 Adhesion Molecules
			10.5.4 Age
			10.5.5 FSH
		10.6 Conclusions
		References
	11: Proteomics of Mammary Gland and Mammary Stem Cells
		11.1 Introduction
		11.2 Cell Types and Specification of the Mammary Gland
		11.3 Mammary Epithelial Cells
		11.4 Adipocytes
		11.5 Fibroblasts
		11.6 Vascular Cells and Immune Cells
		11.7 Proteomics: The Ability to Study Many Proteins Together
		11.8 Quality Control in MS-Based Experiments
		11.9 The Proteome of Bovine Mammary Epithelial Cells
		11.10 MEC Secretome
		11.11 Bioinformatics-Assisted Proteomics
		11.12 Presence of Contaminating Proteins in Cultured Mammary Epithelial or Stem Cell Lines
		11.13 Mammary Epithelial Cell-Derived Exosomes: A Proteomics Analysis
		11.14 Proteomic Analysis of Bovine Mammary Epithelial Cells in Diseases Like Mastitis
		11.15 Mammary Stem Cells (MaSC), Their Identification, and Characterization: Role of Proteomics
		11.16 Characterization of Bovine MaSCs/Progenitor Cells
		11.17 The Secretome from Bovine Mammosphere-Derived Cells (MDCs)
		11.18 Protein Isoforms in MSC
		11.19 Chromatin Organization, Epigenomics and Protein Expression in Mammary Gland Cells
		References
Part III: Therapeutic Applications
	12: Advancing Quantitative Stem Cell Dosing for Veterinary Stem Cell Medicine
		12.1 Introduction
		12.2 Therapeutic Tissue Stem Cells in Animal Tissues
		12.3 Therapeutic M[S]Cs in Veterinary Medicine
		12.4 Previous Attention to Indicators of Stem Cell Dose in Veterinary M[S]C Treatments
		12.5 The Tissue Stem Cell Counting Problem
		12.6 A Solution for the Tissue Stem Cell Counting Problem
		12.7 Benefits of Quantitative Stem Cell Dosing for Stem Cell Veterinary Medicine
		12.8 Conclusions and Future Perspective
		References
	13: Mesenchymal Stem Cells: A Novel Therapy for the Treatment of Bovine Mastitis
		13.1 Introduction
			13.1.1 Immunomodulatory and Immunogenic Properties Suggest That Bovine MSC May Be a Useful Therapeutic Strategy for Mastitis
			13.1.2 The Antibacterial Potential of Bovine Fetal Mesenchymal Stem Cells May Play a Crucial Role Against Pathogens-Causing Ma...
		13.2 Safety and Efficacy of a Bovine MSCs Intramammary Therapy Against Experimentally Induced Staphylococcus aureus Clinical M...
		13.3 Conclusions
		References
	14: Therapeutic Applications of Mesenchymal Stem Cells in Canine Diseases
		14.1 Introduction
		14.2 Why MSCs?
		14.3 Characterisation of MSCs
		14.4 Potential Therapeutic Applications
		14.5 Potential Applications in Musculoskeletal Tissues
		14.6 Potential Applications of MSCs in Non-musculoskeletal Tissues
		14.7 Miscellaneous Studies
		14.8 Conclusions
		References
	15: Biomaterials and Scaffolds in Stem Cell Therapy
		15.1 Introduction
		15.2 Biomaterials and Bioscaffolds
			15.2.1 Biomaterials Used in Stem Cell Culture
				15.2.1.1 Natural Biomaterials in Stem Cell Culture
				15.2.1.2 Synthetic Biomaterials in Stem Cell Culture
				15.2.1.3 Synthetic Polymers in Stem Cell Culture
				15.2.1.4 Mesh Scaffolds in Stem Cell Culture
		15.3 Composite Mesh, Absorbable Synthetic Mesh, and Biological Graft
		15.4 Delivery of Stem Cells Through Biomaterials
		15.5 Clinical Applications of Biomaterials and Scaffolds
		15.6 Conclusions
		References
	16: Prospects of Mesenchymal Stem Cell Secretome in Veterinary Regenerative Therapy
		16.1 Introduction
		16.2 MSCs Secretome or Conditioned Media (CM)
			16.2.1 Extracellular Vesicles
		16.3 Isolation of Conditioned Media
		16.4 Isolation of Exosomes
		16.5 Mechanism of CM in Wound Healing
		16.6 Exosomes as Drug Delivery Agents
		16.7 Clinical Applications of MSCs-CM
			16.7.1 Bone Regeneration/Fracture Healing
			16.7.2 Tendon and Ligament Repair
			16.7.3 Repair of Nerve Injury or Paralysis
			16.7.4 Wound Healing and Hair Follicle Regeneration
		16.8 Conclusion
		References
	17: Reprogramming and Induced Pluripotent Stem Cells in Porcine
		17.1 Introduction
		17.2 Brief History Toward the Generation of Induced Pluripotent Stem Cells
		17.3 Basis of Reprogramming Using Genetic Factors
			17.3.1 Role of Individual Factors in Reprogramming
			17.3.2 Genome-Wide Sequential Events for Establishment and Maintenance of Pluripotency by OSKM Cocktail
				17.3.2.1 Somatic Program Silencing
				17.3.2.2 Stem Cell Program Activation
				17.3.2.3 Re-organization of Chromatin Architecture
			17.3.3 Kinetics of Molecular Signatures During Somatic Cell Reprogramming
			17.3.4 Elite and Stochastic Models for Induced Pluripotent Stem Cell Generation
		17.4 Porcine-Induced Pluripotent Stem Cells
			17.4.1 Choice of Reprogramming Factors
			17.4.2 Choice of the Delivery System
			17.4.3 Choice of Somatic Cells to Be Reprogrammed
			17.4.4 Culture Supplementation with Special Reference to LIF and FGF2
			17.4.5 Culture of iPS with or Without Feeder Cells
			17.4.6 Expression of Marker Genes in Porcine iPS Cells
			17.4.7 In Vitro Lineage Differentiation of Porcine iPS Cells
			17.4.8 Assay for Testing Developmental Potential
				17.4.8.1 Tetraploid Complementation Assay
				17.4.8.2 Teratoma Formation with Porcine iPS Cells
				17.4.8.3 Contribution of Porcine iPS Cells to Chimera Formation
			17.4.9 Naïve Versus Primed iPS Cells
			17.4.10 Other Features of Porcine iPS Cells
		17.5 Therapeutic and Other Applications of Porcine iPS Cells
		17.6 Concluding Remarks
		References
	18: CRISPR/Cas System and Stem Cell Editing: Prospects and Possibilities in Veterinary Sciences
		18.1 Introduction
		18.2 CRISPR/Cas as Genetic Manipulation Tool: An Overview
		18.3 Urgencies of a Typical CRISPR/Cas-Based Genetic Manipulation
			18.3.1 Selection of Effector Cas Protein
			18.3.2 The sgRNA Designing
			18.3.3 The Homology Repair Template
			18.3.4 The Delivery of the CRISPR/Cas Machinery Inside the Cell
		18.4 CRISPR/Cas Tools Use in Stem Cell Technologies: Applications in the Veterinary World
			18.4.1 CRISPR-Based Reprogramming and Directed Differentiation of Pluripotent Stem Cells
			18.4.2 CRISPR-Based Stem Cell Modulation: Scope in Veterinary Sciences
				18.4.2.1 Generation of Genetically Modified Animals with Improved Productivity and Fitness
				18.4.2.2 Animal Health Improvement
					Disease-Resistant Transgenic Animals
					Regenerative Veterinary Medicine
				18.4.2.3 Animal Modeling for Biomedical Research
		18.5 Conclusion
		References
Part IV: Issues and Perspectives
	19: Identification of Species-Specific Stem Cells and Challenges
		19.1 Introduction to Stem Cells
		19.2 Markers of Stem Cells
		19.3 Difficulty in Identifying Stem Cells
		19.4 Challenges of Stem Cell Research
		19.5 Conclusions
		References
	20: Regulations of Animal Cell-Based Drugs in Veterinary Regenerative Medicine
		20.1 Overview of FDA´s Drug Approval Process
		20.2 Centre for Veterinary Medicine (CVM), USA
		20.3 European Union
			20.3.1 Law Governing the Implementation of New Veterinary Medicine Regulations
		20.4 India´s Regulations on Animal Stem Cell Therapy
		References