Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in Labrador retrievers

Abstract

 

Stem Cells in Veterinary Medicine—Current State and Treatment Options

Abstract

Regenerative medicine is a branch of medicine that develops methods to grow, repair, or replace damaged or diseased cells, organs or tissues. It has gained significant momentum in recent years. Stem cells are undifferentiated cells with the capability to self—renew and differentiate into tissue cells with specialized functions. Stem cell therapies are therefore used to overcome the body’s inability to regenerate damaged tissues and metabolic processes after acute or chronic insult. The concept of stem cell therapy was first introduced in 1991 by Caplan, who proposed that massive differentiation of cells into the desired tissue could be achieved by isolation, cultivation, and expansion of stem cells in in vitro conditions. Among different stem cell types, mesenchymal stem cells (MSC) currently seem to be the most suitable for therapeutic purposes, based on their simple isolation and culturing techniques, and lack of ethical issues regarding their usage. Because of their remarkable immunomodulatory abilities, MSCs are increasingly gaining recognition in veterinary medicine. Developments are primarily driven by the limitations of current treatment options for various medical problems in different animal species. MSCs represent a possible therapeutic option for many animal diseases, such as orthopedic, orodental and digestive tract diseases, liver, renal, cardiac, respiratory, neuromuscular, dermal, olfactory, and reproductive system diseases. Although we are progressively gaining an understanding of MSC behavior and their mechanisms of action, some of the issues considering their use for therapy are yet to be resolved. The aim of this review is first to summarize the current knowledge and stress out major issues in stem cell based therapies in veterinary medicine and, secondly, to present results of clinical usage of stem cells in veterinary patients.

Partial Cranial Cruciate Ligament Tears Treated with Stem Cell and Platelet-Rich Plasma Combination Therapy in 36 Dogs: A Retrospective Study

Affiliations 

Abstract

Objective: To evaluate outcomes in 36 dogs with a partial cranial cruciate ligament (CCL) tear treated with autologous bone marrow aspirate concentrate (BMAC) or adipose-derived progenitor cells (ADPC) with platelet-rich plasma (PRP) combination.

Materials and methods: Medical records of client-owned dogs diagnosed with an early partial (≤50%) tear of the craniomedial band of the CCL that was treated with BMAC-PRP or ADPC-PRP were reviewed from 2010 to 2015. Signalment, medical history, physical and orthopedic examination, objective temporospatial gait analyses, radiographs, day 0 and day 90 diagnostic arthroscopy findings, treatment, and outcome were among the data collected. A functional owner questionnaire, including the validated Helsinki chronic pain index (HCPI), was sent to owners whose dog was known to not have had a tibial plateau leveling osteotomy (TPLO). Statistical analysis was performed on data, where significance was established at p < 0.05.

Results: Stifle arthroscopy findings at 90 days posttreatment were available on 13 of the 36 dogs. In nine dogs, a fully intact CCL with marked neovascularization and a normal fiber pattern was found with all previous regions of disruption healed. One dog revealed significant improvement and received an additional injection. The remaining three dogs had a >50% CCL tear, and a TPLO was performed. Four additional dogs were known to have had a TPLO performed elsewhere. Baseline and day 90 posttreatment objective gait analyses were available on 11 of the 36 dogs. A significant difference was found between the treated limb total pressure index percent (TPI%) at day 0 and day 90 (p = 0.0124), and between the treated limb and contralateral limb TPI% at day 0 (p = 0.0003). No significant difference was found between the treated limb and contralateral limb TPI% at day 90 (p = 0.7466). Twelve questionnaires were returned, of which eight were performance/sporting dogs. Seven of the eight had returned to sport; the remaining dog had just begun a return to sport conditioning program 6 months posttreatment. All 12 respondents believed that their dog had an excellent or very good quality of life and rated their dog’s procedural outcome as excellent or good.

Conclusion: The use of BMAC-PRP and ADPC-PRP shows promise for the treatment of early partial CCL tears in dogs. Further studies are needed and should be randomized, blinded, and controlled.

pet allergies

Case report on the use of Stem Cells for Feline IBD

New Treatment Option for Feline IBD

 

Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis

Associated Data

Supplementary Materials

Abstract

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune‐mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose‐derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti‐fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710–1722

Keywords: Adipose‐derived stem cells, Fresh, Allogeneic, Cats, Gingivostomatitis, Oral Mucosa, Immunomodulation