Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes

Pérez-Merino, Eva M.; Usón-Casaús, Jesús M; Zaragoza, Concepción; Duque, Javier; Mariñas-Pardo, Luis; Hermida-Prieto, Manuel; Barrera-Chacón, Rafael; Gualtieri, M.

doi:10.1016/j.tvjl.2015.08.003

Cited by 73 publications

(63 citation statements)

References 34 publications

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“…Recently, a number of studies have shown that MSCs can effectively ameliorate IBD in rodent models (Gonzalez-Rey et al, 2009;Tanaka et al, 2008;Wang et al, 2014). Furthermore, administering MSCs as a therapeutic option for IBD in small clinical trials (both in humans and dogs) has also shown considerable promise (Kim et al, 2017;Perez-Merino et al, 2015). Our previous studies have demonstrated that TSG-6 released from human and canine MSCs plays a crucial role in immunomodulation by inducing an M2 macrophage switch Song et al, 2017b).…”

Section: Discussionmentioning

confidence: 99%

Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

Song

Ryu

et al. 2019

Research in Veterinary Science

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A B S T R A C TCanine inflammatory bowel disease (IBD) is an intractable autoimmune disorder that results in various gastrointestinal and systemic symptoms. Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. Furthermore, although it is known that MSCs pre-treated with pro-inflammatory cytokines show enhanced anti-inflammatory properties via the secretion of soluble factors, the underlying mechanisms of IBD remain unclear. The aim of this study was to demonstrate the therapeutic effects and corresponding mechanisms of canine adipose tissue-derived (cAT)-MSCs stimulated with TNF-α in mouse models of IBD. Mice with dextran sulfate sodium (DSS)-or dinitrobenzene sulfonic acid (DNBS)-induced colitis were injected intraperitoneally with cAT-MSCs pre-treated with TNF-α. Colitis severity was assessed and colon tissues were collected for histopathological, enzyme-linked immunosorbent assay, and flow cytometry analysis. cAT-MSCs stimulated with TNF-α secreted higher concentrations of immunomodulatory factors such as TSG-6 and PGE2, which play a key role in inducing phenotypic alterations in macrophages. Consequently, TNF-α-pre-treated cAT-MSCs further regulated colonic inflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-10, and ameliorated DSS-or DNBS-induced colitis in mice. Additionally, we demonstrated that M1 macrophages (F4/80 + /iNOS + cells) were decreased in colon tissues from mice treated with TNF-α-pre-treated cAT-MSCs, whereas M2 macrophages (F4/80 + /CD206 + cells) were increased. These results may suggest a new cell-based therapeutic option for treating IBD.

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Section: Discussionmentioning

confidence: 99%

Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

Song

Ryu

et al. 2019

Research in Veterinary Science

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“…In this patient population, ASC fistula injections increased the rate of fistula closure as assessed clinically and by MRI and even reduced the median time to clinical remission in one placebo‐controlled study (Fig. E) . In most of these studies, at least 50% of patients treated with ASC had complete closure of the treated fistula at the final time point of 240 days.…”

Section: Resultsmentioning

confidence: 88%

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

et al. 2018

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The objective of this Review is to describe the safety and efficacy of adipose stem/stromal cells (ASC) and stromal vascular fraction (SVF) in treating common diseases and the next steps in research that must occur prior to clinical use. Pubmed, Ovid Medline, Embase, Web of Science, and the Cochrane Library were searched for articles about use of SVF or ASC for disease therapy published between 2012 and 2017. One meta-analysis, 2 randomized controlled trials, and 16 case series were included, representing 844 human patients. Sixty-nine studies were performed in preclinical models of disease. ASCs improved symptoms, fistula healing, remission, and recurrence rates in severe cases of inflammatory bowel disease. In osteoarthritis, ASC and SVF improved symptom-related, functional, radiographic, and histological scores. ASC and SVF were also shown to improve clinical outcomes in ischemic stroke, multiple sclerosis, myocardial ischemia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, chronic liver failure, glioblastoma, acute kidney injury, and chronic skin wounds. These effects were primarily paracrine in nature and mediated through reduction of inflammation and promotion of tissue repair. In the majority of human studies, autologous ASC and SVF from liposuction procedures were used, minimizing the risk to recipients. Very few serious, treatment-related adverse events were reported. The main adverse event was postprocedural pain. SVF and ASC are promising therapies for a variety of human diseases, particularly for patients with severe cases refractory to current medical treatments. Further randomized controlled trials must be performed to elaborate potential safety and efficacy prior to clinical use. Stem Cells 2018;36:1311-1328.

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“…MSCs have been used in animal model of colitis successfully in pre-clinical studies (González et al, 2009). MSCs have shown immunomodulatory and anti-inflammatory effects in experimental colitis and successful clinical results have been achieved in humans with CD and UC (Pérez-Merino et al, 2015).…”

Section: Mesenchymal Stem Cell Treatmentmentioning

confidence: 99%

“…In veterinary medicine, a recent study of the use of intravenous MSC therapy in spontaneous feline enteropathy was showed a positive and safe clinical response (Pérez-Merino et al, 2015).…”

Section: Mesenchymal Stem Cell Treatmentmentioning

confidence: 99%

Inflammatory Bowel Disease and Current Treatment Options in Dogs

Arslan¹

2017

American Journal of Animal and Veterinary Sciences

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Inflammatory Bowel Disease (IBD) is an idiopathic and chronic gastrointestinal failure of cats, dogs and some farm animals such as horses. Since the long and difficult classical therapy of the disease has various side effects such as malignancy and lymphoma, new therapeutic methods are needed. However, a safe and standardized treatment protocol has not been developed, yet. Therefore, IBD treatment is still a big dilemma for both veterinary and human medicine. In this review, IBD and new possible therapeutic alternatives were evaluated for dogs.

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Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes

Cited by 73 publications

References 34 publications

Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

Inflammatory Bowel Disease and Current Treatment Options in Dogs

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