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

Abstract

Systemic administration of mesenchymal stem cells (MSCs) has been shown to be safe and efficacious in humans with Crohn's disease. The aim of this study was to evaluate the safety of an intravenous (IV) infusion of adipose tissue-derived mesenchymal stem cells (ASCs) and to assess macroscopic and histological effects in the digestive tract of dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received a single ASC infusion (2 × 10(6) cells/kg bodyweight). Full digestive endoscopic evaluation was performed pre-treatment and between 90 and 120 days post-treatment with mucosal changes being assessed using a fit-for-purpose endoscopic scale. Endoscopic biopsies from each digestive section were evaluated histologically according to the World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group criteria. The pre- and post-treatment canine IBD endoscopic index (CIBDEI) and histological score (HS) were calculated and compared using the Wilcoxon test. Remission was defined as a reduction of >75% of the CIBDEI and HS compared with pre-treatment. No acute reactions to ASC infusion or side effects were reported in any dog. Significant differences between pre- and post-treatment were found in both the CIBDEI (P = 0.004) and HS (P = 0.004). Endoscopic remission occurred in 4/11 dogs with the remaining dogs showing decreased CIBDEI (44.8% to 73.3%). Histological remission was not achieved in any dog, with an average reduction of the pre-treatment HS of 27.2%. In conclusion, a single IV infusion of allogeneic ASCs improved gastrointestinal lesions as assessed macroscopically and slightly reduced gastrointestinal inflammation as evaluated by histopathology in dogs with IBD.

Inflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same?

“…One study has been published in dogs with NRE, with 8 out 11 dogs in remission (decrease in CIBDAI of more than 75%) at the end of the study (Perez‐Merino et al . ). Although this study was short (42 days), these are very promising results and further research in this domain is expected.…”

“…Their effects rely on regenerative as well as anti-inflammatory properties. One study has been published in dogs with NRE, with 8 out 11 dogs in remission (decrease in CIBDAI of more than 75%) at the end of the study (Perez-Merino et al . 2015 ).…”

Correlation between canine inflammatory bowel disease activity indices after stem cell therapy

“…However, although stem cells seemed to be more effective in recovering both macroscopic and histological architecture than the standard treatment (Perez-Merino and others 2015a), the non-correlation between mucosal healing and clinical signs still persisted. Recently, Minamoto and others (2015) showed that clinical improvement after standard therapy in dogs with IBD was also not accompanied by significant changes in the faecal microbiota, suggesting the presence of oxidative stress in clinically responsive patients.…”

“…Although adipose-derived stem cells (ASCs) have recently been demonstrated to improve clinical, endoscopic and histological signs of canine IBD (Perez-Merino and others 2015a, b), the agreement between the clinical response and the degree of mucosal healing after this new therapy has never been investigated and would indicate its true degree of effectiveness. Thus, the authors’ aim was to assess the correlation between clinical, endoscopic and histological activity in dogs with IBD treated with stem cells.…”

Isolation and Cryopreservation of Animal Mesenchymal Stromal Cells

“…In recent years, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have atracted much atention due to their potential use in regenerative medicine and tissue engineering as shown by the main applications described in the literature and the noteworthy progress that has been made toward their beter understanding and characterization [2]. Those cells display a signiicant therapeutic plasticity as relected by their advantageous characteristics: the ability to enhance tissue renovation, the immunomodulatory, and anti-inlammatory efects [3,4] and the possibility to be used for both autologous and allogeneic therapies [5].…”