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Canine Wharton’s JellyDerived Mesenchymal Stem Cells. Cell Transplant 21 (2012): 1493-1502. 17. Zucconi E, Vieira NM, Bueno CR, et al. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy. J. Biomed. Biotechnol (2011): 1-9. 18. Martin DR, Cox NR, Hathcock TL, et al. Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow. Exp. Hematol 30 (2002): 879-886. 19. Quimby JM, Borjesson DL. Mesenchymal stem cell therapy in cats: Current knowledge and future potential. J. Feline Med. Surg 20 (2018): 208-216. 20. Vidane AS, Souza AF, Sampaio RV, et al. Cat amniotic membrane multipotent cells are nontumorigenic and are safe for use in cell transplantation. Stem Cells Cloning Adv. Appl 7 (2014): 71-78. 21. De Schauwer C, Meyer E, Cornillie P, et al. Optimization of the Isolation, Culture, and Characterization of Equine Umbilical Cord Blood Mesenchymal Stromal Cells. Tissue Eng. Part C Methods 17 (2011): 1061-1070. 22. Jäger M, Bachmann R, Scharfstädt A. et al. Ovine Cord Blood Accommodates Multipotent Mesenchymal Progenitor Cells. In Vivo 11 (2006). 23. Kang JG, Park SB, Seo MS, et al. Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood. J. Vet. Sci 14 (2013): 367. 24. Kumar K, Agarwal P, Das K, et al. Isolation and characterization of mesenchymal stem cells from caprine umbilical cord tissue matrix. Tissue Cell 48 (2016): 653-658. 25. Nazari-Shafti TZ, Bruno IG, Martinez RF, et al. High Yield Recovery Challenges of stem cell therapies in companion animal practice Regenerative Medicine Author Contributions Conceptualization: Kang MH, Park HM; Data curation: Kang MH; Investigation: Kang MH, Park HM; Supervision: Park HM; Writing - original draft: Kang MH, Park HM; Writing - review & editing: Kang MH, Park HM. Although MSCs from various sources share many biological features and characteristics, differences have been reported in their immunophenotype, proliferative capacity, differentiation potential, immune modulation and gene expression profiles [1,16,17]. Consequently, the application and effectiveness of each type in veterinary clinical practice may differ [18,19]. Even though stem cell treatment has potential benefits, the true therapeutic efficacy and adverse effects of stem cell therapy are not fully understood [12,13,20]. Several studies have suggested the possibility of adverse reactions during intravenous stem cell transplantation [13,20,21]. Additionally, many veterinary stem-cell treatments studies contain design flaws that limit the reliability of the results. For example, some failed to maintain consistent therapeutic protocols and lacked control groups or blinded evaluation [22-26]. Most recent stem cell reviews in veterinary medicine describe animal models for stem cell research for human disease. These studies mainly focused on various stem cell types and their potencies [27-29]. Expanded cell types and treatment protocols have been tested in canine models for clinical application in both humans and animals. Only one literature review describes the clinical use of AD-MSCs for spontaneous animal disease [19]. Before stem cells can be used in companion animal treatment, their safety and efficacy should be proven. The present literature review focuses on the clinical application of cell-based treatment for spontaneous diseases of different organ system in dogs and cats. To determine the status, challenges, and future prospects of stem cell therapy in veterinary medicine, we analyzed some of the most relevant clinical studies, and investigated treatment and evaluation methods. BASICS OF STEM CELL TRIALS It is well known that stem cells are unspecialized cells with the ability to self-renewal and differentiation of specialized cell types [1,28]. Regenerative medicine using stem cells was first used to treat hematologic diseases via bone marrow transplantation in late 1900s [30]. By 2000, the utility of stem cells had expanded to include non-hematologic disease such as cardiologic and neurologic diseases [5,10,31-33]. Stem cells can be classified under 2 large categories based on their sources: embryonic stem cells (ESCs) and adult stem cells (ASCs) [34]. ESCs have more developmental possibility than ASCs, but these stem cells have ethical and legal issues and safety concerns, including tumorigenicity [35]. ASCs can derived from bone marrow, peripheral blood, umbilical cord blood and tissue, adipose tissue, skin, neuron and muscle [1]. Recently, it has been discovered that pluripotent stem cells can be generated directly from adult somatic cells via genetic reprogramming. There are known as induced pluripotent stem cells (iPSCs) [36]. Stem cell treatment involves using stem cells to treat various disease or conditions. Stem cells are collected, transformed into specific types of cells via cell culture, and transplanted into the body. The stem cells and their derivatives then replace and heal damaged tissues. The curative effects of stem cell treatment can be evaluated differently depending on the primary disease, though it is typically accomplished by testing the structural and functional restoration of the target organ (Fig. 1) [34].
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