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healing for a wide variety of cellular types. This includes cartilage repair, angiogenesis in osteoarthritis, tendon defects, ligament tissue, intervertebral disk repair, ischemic heart tissue, graft-versus-host disease, and osteogenesis imperfecta.6,9-21 Of particular interest in musculoskeletal medicine is the observation in degenerative diseases, such as advanced osteoarthritis, that an individual’s local adult stem cell frequency and potency may be depleted, with reduced proliferative capacity and ability to differentiate.22,23 It has been suggested that addition of these missing stem cell elements might help these conditions. Studies have demonstrated such improvement with adult stem cell therapy by successful regeneration of osteoarthritic damage and articular cartilage defects.24,25 AD-SC Use in Human Cosmetic Surgery Cosmetic-plastic surgeons have studied, and safely and successfully utilized, autologous fat grafting for structural augmentation via transplantation of lipoaspirants for many years. In the past decade, better understanding of the cellular mechanisms responsible for successful soft tissue augmentation has been better defined, focusing on the plentiful undifferentiated stem/stromal elements rather than the survival of mature adipocytes.26 During the 1990s, further understanding and enhancements by cosmetic plastic surgeons to improve the “take” of fat grafts led to the effective addition of high-density, platelet-rich plasma (HDPRP) concentrates to further enhance the success of autologous fat grafts (AFG).27 Several publications within the human cosmeticplastic surgical literature have reported significant contributions to successful adipose tissue transplantation when these autologous grafts were blended with highly concentrated platelet elements (PRPs).28-30 Recognition of the significant clinical contribution to structural fat grafting when transplanted with the multitude of platelet-derived growth factors, cytokines, and chemokines, became a valuable aid in retaining improved structural augmentation. It is believed that these effects are largely a result of provision of a undifferentiated cell population and HDPRP’s ability to improve active angiogenesis, stimulation and promotion of undifferentiated cell adherence, proliferation, and differentiation activities of precursor cells in the grafts, reflecting the niche in which they are received (Figure). Figure. Photomicrograph of adipose-derived MSCs treated with PRP in vitro Discovery of Mesenchymal Stem Cells July/August 2011 Today’s Veterinary Practice 29 Advances in Stem Cell Therapy | Research At This Point in Time When adipose-derived stem cells are placed within osteoarthritic degenerated cartilage, chondrogenic differentiation is believed to be encouraged.31-34 In the 1990s, Young, et al, showed repair of an Achilles tendon tear when placed in a collagen matrix, then placed in a tendon defect.35 In 2003, Murphy, et al, reported significant improvement in medial meniscus and cartilage regeneration with autologous stem cell therapy in an animal model. Not only was there evidence of marked regeneration of meniscal tissue, but the usual progressive destruction of articular cartilage, osteophytic remodeling, and subchondral sclerosis commonly seen in osteoarthritic disease was reduced in MSC-treated joints compared with controls.36 In 2008, Centeno, et al, reported significant knee cartilage growth and symptom improvement in a human case report using cultureexpanded autologous MSCs from bone marrow.37 In 2010, Little, et al, demonstrated the successful differentiation of human AD-SCs to ligamental tissue following placement in a simulated ligament matrix composed of native ligamentous material combined with collagen fibrin gel. Cells placed in this manner showed changes in gene expression consistent with ligament growth and expression of a ligament phenotype.38 In 2011, Albano and Alexander successfully reported an autologous fat graft as a mesenchymal stem source and living bioscaffold (autologous regenerative matrix) to repair a persistent patellar tendon tear.133 Growth factors and chemical elements, such as present in HDPRP, are believed to provide favorable influences within the microenvironment to enhance adherence, proliferation, differentiation and migration of cells towards this end.39 Continuing Research There are more than 43 ongoing U.S. human controlled clinical trials with approximately half of them still recruiting participants.40 Studies include the use of AD-SCs for degenerative arthritis. In that trial, AD-SCs will be culture expanded, then administered into a cartilage tissue lesion via orthopedic surgery.41 Anothertrialpending(ScarponeandAlexander, sponsored by Trinity Health Systems) explores the use of PRPs alone versus AD-SC alone versus PRPs and AD-SCs together. A similar planned veterinary study will also explore PRP with and without AD-SCs. Other ongoing human studies include AD-SCs for the treatment of diabetes, rectovaginal and perianal fistulas, peripheral vascular disease, ischemic heart disease, coronary arteriosclerosis, hemifacial atrophy, liver cirrhosis, breast reconstruction after breast cancer, anti-aging, polycystic ovary syndrome, metabolic syndrome X, fecal incontinence, graft versus host disease, chronic critical limb ischemia in diabetic patients,
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