Vet J. 2015 Dec;206(3):385-90. doi: 10.1016/j.tvjl.2015.08.003. Epub 2015 Aug 7.
Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs withinflammatory bowel disease: Clinical and laboratory outcomes.
1Department of Animal Medicine and Surgery, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain. Electronic address: firstname.lastname@example.org.
2Department of Animal Medicine and Surgery, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain.
3Veterinary Teaching Hospital, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain.
4Centauri Biotech Company, 15142 Arteixo, A Coruña, Spain.
5Department of Health Animal Science and Food Safety, Section of Surgery, Veterinary Faculty, Via Celoria, 10. 20133 Milan, Italy.
Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn’s disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD.
KEYWORDS: Albumin; Canine; Clinical activity index; Inflammatory bowel disease; Mesenchymal stem cell; Treatment
Mesenchymal stem cell therapy for inflammatory bowel diseases: promise and challenge.
1Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. email@example.com.
Inflammatory Bowel Disease (IBD) is a complicated disease that arises as a consequence of the interaction among environment, genetic factors and autoimmunity. Available therapeutic interventions with pharmacological or biological drugs have a very selective action. Mesenchymal stem cells (MSCs) have been emerging as a promising cellular therapy for the treatment of IBD due to their multifaceted functions. This article summarizes recent progress in both preclinical studies and clinical trials employing MSCs in IBD treatment. We justify the use of MSC-based cell therapy as a novel strategy for IBD, discuss the biological roles that MSCs play underlying their therapeutic effects focusing on their immune-suppressive effects, illustrate methods to improve MSCs for better repair, and pinpoint the obstacles hindering their success and the challenges to overcome before their ultimate application.
Keywords: Immunomodulation, inflammatory bowel disease, MSC.
Immunol Lett. 2015 Dec;168(2):191-200. doi: 10.1016/j.imlet.2015.06.018. Epub 2015 Jul 10.
Mesenchymal stromal cells and chronic inflammatory bowel disease.
1Department of Pediatric Hematology-Oncology, IRCCS, Bambino Gesù Children’s Hospital, Rome, Italy.
2Department of Pediatric Hematology-Oncology, IRCCS, Bambino Gesù Children’s Hospital, Rome, Italy; Department of System Medicine, University of Rome “Tor Vergata”, Rome, Italy.
3Department of Pediatric Hematology-Oncology, IRCCS, Bambino Gesù Children’s Hospital, Rome, Italy; Department of Pediatrics, University of Pavia, Italy.
Recent experimental findings have shown the ability of mesenchymal stromal cells (MSCs) to home to damaged tissues and to produce paracrine factors with anti-inflammatory properties, potentially resulting in reduction of inflammation and functional recovery of the damaged tissues. Prompted by these intriguing properties and on the basis of encouraging preclinical data, MSCs are currently being studied in several immune-mediated disorders. Inflammatory bowel diseases (IBD) represent a setting in which MSCs-based therapy has been extensively investigated. Phase I and II studies have documented the safety and feasibility of MSCs. However, efficacy results have so far been conflicting. In this review, we will discuss the biologic rationale that makes MSCs a promising therapeutic tool for IBD, and analyze recent experimental and clinical findings, highlighting current limitations and future perspectives of MSCs-related immunotherapy for IBD.
KEYWORDS: Cell therapy; Crohn’s disease; Inflammatory bowel disease; Mesenchymal stromal cells; Regenerative medicine; Translational research; Ulcerative colitis