Therapeutic Applications of Mesenchymal Stem Cells in Veterinary Medicine

Preface
Contents
About the Author
Abbreviations
1: Mesenchymal Stem Cells Therapeutic Applications in Cartilage Regeneration
	1.1 Introduction
	1.2 In Vitro Studies
		1.2.1 MSCs and Chondrogenesis
		1.2.2 Effect of Growth Factors and Chemicals
		1.2.3 Scaffolds and MSCs Chondrogenesis
		1.2.4 Combined Extrinsic Factors and MSCs Chondrogenesis
		1.2.5 Chondrocytes, Hypoxia and MSCs Chondrogenesis
		1.2.6 Donor Factors Affecting MSCs Chondrogenesis
		1.2.7 Miscellaneous Factors
	1.3 Challenges in MSCs Therapy
	1.4 In Vivo Studies
		1.4.1 Sheep Studies
			1.4.1.1 Chondral Defect Models
			1.4.1.2 Full-Thickness Osteochondral Defect Models
			1.4.1.3 Cruciate Ligament and Medial Meniscectomy Model
			1.4.1.4 Comparative Studies
			1.4.1.5 Meniscectomy Model
			1.4.1.6 Miscellaneous Models
		1.4.2 Goat Studies
		1.4.3 Dog Studies
			1.4.3.1 Experimental Studies
				1.4.3.1.1 Chondral and Osteochondral Defect Models
				1.4.3.1.2 Chondral Defects
				1.4.3.1.3 Osteochondral Defects
				1.4.3.1.4 Osteonecrosis
				1.4.3.1.5 Cruciate Ligament Resection Model
				1.4.3.1.6 Meniscectomy Model
			1.4.3.2 Clinical Trials/Studies
				1.4.3.2.1 Cell Transplantation, Concentration and Frequency
				1.4.3.2.2 Results
		1.4.4 In Vivo Horse Studies
			1.4.4.1 Safety of Intra-articular Transplantation of MSCs
			1.4.4.2 Experimental Studies
			1.4.4.3 Clinical Studies
				1.4.4.3.1 Cell Transplantation, Concentration and Frequency
				1.4.4.3.2 Results
	1.5 Conclusion(s)
	References
2: Mesenchymal Stem Cells Therapeutic Applications in Bone Regeneration
	2.1 Introduction
	2.2 Why Mesenchymal Stem Cells for Bone Regeneration
	2.3 In Vitro Osteogenesis of MSCs
		2.3.1 Growth Factors and MSCs Osteogenesis
		2.3.2 Scaffold and MSCs Osteogenesis
		2.3.3 Mechanical Factors
		2.3.4 Tissue Source and MSCs Osteogenesis
		2.3.5 Miscellaneous Factors and MSCs Osteogenesis
	2.4 Fracture Healing (FH) Model Study
	2.5 In Vivo Osteogenic Studies
		2.5.1 Sheep MSCs Osteogenic Studies
			2.5.1.1 Tibial Defect Model
			2.5.1.2 Spinal Fusion Models
			2.5.1.3 Metatarsal Bone Defects
			2.5.1.4 Femoral Bone Defect Models
			2.5.1.5 Cranial Bone Defect Models
			2.5.1.6 Osteoporotic Bone Model
		2.5.2 Goat Experimental Bone Defect Models
			2.5.2.1 Tibial Bone Defect Models
			2.5.2.2 Femoral Bone Defect Models
			2.5.2.3 Maxillary Sinus Models
		2.5.3 Dog Experimental Bone Defect Models
			2.5.3.1 Femoral Bone Defect Model
			2.5.3.2 Radial Bone Defect Model
			2.5.3.3 Mandibular Bone Defect Models
			2.5.3.4 Ulnar Bone Defect Model
		2.5.4 Dog In Vivo Clinical Studies
		2.5.5 Horse In Vivo Experimental Studies
		2.5.6 Horse In Vivo Clinical Studies
	2.6 Conclusion(s)
	References
3: Mesenchymal Stem Cell Therapeutic Applications in Muscle, Tendon and Ligament Regeneration
	3.1 Introduction
	3.2 In Vitro Studies
		3.2.1 Tendon Stem Cells Vs. Non-tendon MSCs
		3.2.2 Tenogenic Differentiation
		3.2.3 Growth Factors and MSCs/TSPCs Tenogenesis
		3.2.4 Matrices/Scaffolds and MSCs Tenogenesis
		3.2.5 Miscellaneous Factors Affecting MSCs Tenogenesis
	3.3 Muscular Disorders
		3.3.1 In Vitro Muscle Differentiation Studies
	3.4 MSCs Therapeutic Effects
	3.5 In Vivo MSCs Studies
		3.5.1 Route of Implantation
		3.5.2 Sheep Studies
			3.5.2.1 Tendon
		3.5.3 Dog Studies
			3.5.3.1 Experimental Studies
			3.5.3.2 Clinical Studies
				3.5.3.2.1 Tendon Studies
				3.5.3.2.2 Ligament Studies
				3.5.3.2.3 Muscle Studies
		3.5.4 Horse Studies
			3.5.4.1 Experimental Studies
				3.5.4.1.1 Tendon Studies
				3.5.4.1.2 Ligament Study
			3.5.4.2 Clinical Studies
				3.5.4.2.1 Tendon Injuries
				3.5.4.2.2 Ligament Injuries
				3.5.4.2.3 Mixed Tendon and Ligament Injury Studies
	3.6 Conclusions
	References
4: Mesenchymal Stem Cells Therapeutic Applications in Peripheral Nervous System Disorders
	4.1 Introduction
	4.2 Peripheral Nerve Injury
	4.3 Nerve Homeostasis Potential
	4.4 Surgical Procedure and Limitations Thereof
	4.5 Why MSCs in PNI?
	4.6 In Vivo Experimental Studies
		4.6.1 Peripheral Nerve Injury Models
		4.6.2 Large Animal Peripheral Nerve Resection Models
			4.6.2.1 Sciatic Nerve Resection Model
			4.6.2.2 Miscellaneous Nerve Resection Models
	4.7 Conclusion(s)
	References
5: Mesenchymal Stem Cells Therapeutic Applications in Central Nervous System Disorders
	5.1 Introduction
	5.2 Regeneration Potential of PNS vs. CNS
		5.2.1 In Vitro MSCs Neurogenic Studies
		5.2.2 Neural-Like Cell Morphology, Expression Analysis and Electrical Activity
		5.2.3 MSCs Source-Based Differences and Activity in Disease
		5.2.4 Conflicting Reports
	5.3 In Vivo Studies
		5.3.1 Neurological Affections and MSCs Mechanism of Actions
		5.3.2 Meningoencephalomyelitis of Unknown Origin (MUO)
		5.3.3 Canine Distemper (CD)
		5.3.4 Myelomeningocele (MMC)
		5.3.5 Global Hypoxia Injury
		5.3.6 Parkinson´s Disease (PD)
		5.3.7 Intervertebral Disc Disease (IVDD)
			5.3.7.1 MSCs Dose and Survival
			5.3.7.2 Goat Studies
			5.3.7.3 Sheep Studies
		5.3.8 Spinal Cord Injury (SCI)
			5.3.8.1 Experimental SCI Studies
			5.3.8.2 Comparative Studies
			5.3.8.3 MSCs Transfection and SCI Repair
			5.3.8.4 Clinical Intervertebral Disc or Spinal Cord Injury Studies
		5.3.9 Wobbler Syndrome in Horse
	5.4 Conclusion(s)
	References
6: Mesenchymal Stem Cells Therapeutic Applications in Cardiovascular Disorders
	6.1 Introduction
	6.2 Why MSCs?
	6.3 MSCs Cardiogenic Studies
		6.3.1 Differentiation
		6.3.2 Paracrine Actions
	6.4 In Vivo Studies
		6.4.1 Cardiomyopathy
			6.4.1.1 Ischaemic Cardiomyopathy
				6.4.1.1.1 Sheep Studies
				6.4.1.1.2 Dog Studies
			6.4.1.2 Non-Ischaemic Cardiomyopathy
				6.4.1.2.1 Clinical Studies
					6.4.1.2.1.1 Chronic Chagas Cardiomyopathy
					6.4.1.2.1.2 Dilatation Cardiomyopathy (DCM)
					6.4.1.2.1.3 Valvular Diseases
		6.4.2 Cardiac Pacemaker
		6.4.3 Congenital or Acquired Cardiac or Vascular Defects
	6.5 Conclusion(s)
	References
7: Mesenchymal Stem Cells Therapeutic Applications in Gastrointestinal Disorders
	7.1 Introduction
	7.2 MSCs in GIT Affections
	7.3 Oral Cavity
		7.3.1 Experimental Studies
			7.3.1.1 Periodontal Defects
			7.3.1.2 Oral Lesions and Mucosal Ulcers
			7.3.1.3 Vocal Fold Injury and Laryngotracheal Fistula
		7.3.2 Clinical Studies
	7.4 Oesophagus
	7.5 Intestines
		7.5.1 Inflammatory Bowel Disease (IBS)
		7.5.2 Anal Furunculosis/Fistula
		7.5.3 Endotoxaemia
	7.6 Liver
		7.6.1 In Vitro MSC Hepatocyte Differentiation
		7.6.2 In Vivo Liver Studies
			7.6.2.1 Dog Liver Injury Model
			7.6.2.2 Hepatocutaneous Syndrome
			7.6.2.3 Hepatocellular Carcinoma
	7.7 Conclusion(s)
	References
8: Mesenchymal Stem Cells Therapeutic Applications in Lung Disorders
	8.1 Introduction
	8.2 MSCs Therapeutic Effects in Lung Pathologies
	8.3 In Vivo Mesenchymal Stem Cell Studies in Veterinary Species
		8.3.1 MSCs Regenerative Effects
		8.3.2 Sheep Studies
		8.3.3 Cat Studies
		8.3.4 Broncho Pleural Fistula
		8.3.5 Dog Studies
		8.3.6 Horse Studies
			8.3.6.1 Recurrent Airway Obstruction
		8.3.7 MSCs and Respiratory Viral Infection
	8.4 Conclusion(s)
	References
9: Mesenchymal Stem Cells in Reproductive System: Reproductive and Therapeutic Applications
	9.1 Introduction
	9.2 MSCs from Reproductive Organs and Foetal Membranes
	9.3 MSCs Promote Follicular and Embryo Growth
	9.4 MSCs as Nuclear Donor
	9.5 MSC Therapeutic Applications
		9.5.1 Female Reproductive System
			9.5.1.1 Bilateral Ovarian Dystrophy in Cattle
				9.5.1.1.1 Ovum Pick-Up-Induced Lesions
			9.5.1.2 Follicular Cyst
			9.5.1.3 Endometrial Affections
				9.5.1.3.1 Endometriosis
		9.5.2 Male Reproductive System
			9.5.2.1 Transdifferentiation of MSCs into Putative Germ Cells
			9.5.2.2 Semen Cryopreservation
	9.6 Conclusion(s)
	References
10: Mesenchymal Stem Cells Therapeutic Applications in Urinary System Disorders
	10.1 Introduction
	10.2 MSCs in Renal Diseases and Potential Applications
	10.3 In Vivo Studies
		10.3.1 Renal Insufficiency Studies
			10.3.1.1 Sheep Studies
			10.3.1.2 Dog Studies
			10.3.1.3 Cat Studies
		10.3.2 Urinary Bladder
			10.3.2.1 In Vivo Studies
		10.3.3 Urethral Sphincter Deficiency
	10.4 Conclusion(s)
	References
11: Mesenchymal Stem Cells Therapeutic Applications in Integumentary System Disorders
	11.1 Introduction
	11.2 Why Mesenchymal Stem Cell Therapy?
		11.2.1 MSCs Anti-Inflammatory/Immunomodulatory Role
		11.2.2 MSCs Anti-Microbial Role
	11.3 Wound Healing
		11.3.1 Skin Wounds and Their Healing Complicacies in Veterinary Medicine
		11.3.2 In Vivo MSC Wound-Healing Studies
			11.3.2.1 In Vivo Experimental Studies
				11.3.2.1.1 Sheep Model
				11.3.2.1.2 Goat Model
				11.3.2.1.3 Dog Model
				11.3.2.1.4 Horse Model
			11.3.2.2 Clinical Studies on Wound Healing
				11.3.2.2.1 Dog Clinical Studies
				11.3.2.2.2 Equine Clinical Studies
	11.4 Atopic Dermatitis
	11.5 Equine Laminitis
	11.6 Mammary Gland
	11.7 MSCs Posology
	11.8 Conclusion(s)
	References
12: Mesenchymal Stem Cells Therapeutic Applications in Endocrine Disorders
	12.1 Introduction
	12.2 Endocrine Disrupting Chemicals and MSCs
	12.3 Endocrine Disorders and MSCs
	12.4 Metabolic Syndrome
	12.5 MSCs and Diabetes Mellitus (DM)
		12.5.1 In Vitro MSC Studies
		12.5.2 In Vivo Studies
			12.5.2.1 Experimental Studies
			12.5.2.2 Clinical Studies
	12.6 Conclusion(s)
	References
13: Mesenchymal Stem Cells Therapeutic Applications in Eye and Adnexa Ailments
	13.1 Introduction
	13.2 Why Mesenchymal Stem Cell (MSC) Therapy?
	13.3 In Vivo Studies
		13.3.1 Corneal Ailments
			13.3.1.1 Corneal Ulcers
			13.3.1.2 Dog Chronic Superficial Keratitis
			13.3.1.3 Horse Mixed Eye Lesions
			13.3.1.4 Immune-Mediated Keratitis (IMMK)
		13.3.2 Keratoconjunctivitis Sicca (KCS)
		13.3.3 Retinal and Optic Nerve Disorders
			13.3.3.1 Retinal Detachment
			13.3.3.2 Glaucoma
	13.4 Conclusion(s)
	References