Therapeutic Applications of Mesenchymal Stem Cells in Veterinary Medicine

Description

This book reviews the potential therapeutic and reproductive applications of mesenchymal stem cells in veterinary regenerative and reproductive medicine. The systemic approach focuses on musculoskeletal structures like cartilage, bone, muscle, tendon, ligaments and nervous tissues. It also focuses on other body systems like gastrointestinal, cardiovascular, urogenital, respiratory and integumentary system. Besides, the special glands or organs like endocrine glands and eye and its adnexa are also focused. The book chapters discusses the problems and the need for regenerative medicine employing MSCs. It provides an ex vivo basis of MSCs therapeutics and reproductive potential followed by their in vivo applications. The book further provides an understanding on the behavior and mechanisms of action of mesenchymal stem cells. The book also abridges challenges and provides future prospects of mesenchymal stem cells in clinical and reproductive applications. As such, the book offers a valuable resource for students, veterinarians, and scientists working in the regenerative and reproductive sciences in human and 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