Repeated IV stem cell treatment for dogs with chronic gut inflammation

Abstract

<h4>Background</h4>Mesenchymal stromal cells (MSCs) are a promising cell source for the treatment of dogs with refractory chronic inflammatory enteropathy (CIE). Although several clinical trials have reported the beneficial effects of MSCs for CIE, all previous studies were conducted by the same research group using a single intravenous infusion protocol. Because most intravenously infused MSCs rapidly disappear from the body, repeated infusions of these cells at regular intervals may prolong the short-term effects of MSCs. This study evaluated the short-term clinical outcomes and safety of a treatment regimen including repeated intravenous infusions of allogeneic MSCs in dogs with refractory CIE.<h4>Methods</h4>Dogs with refractory CIE received repeated intravenous infusions of 2 × 10⁶ cells/kg of allogeneic adipose-derived MSCs according to the following protocol: twice weekly at 3-4 day intervals for the first 2 weeks, once weekly for the next 2 weeks, and once every 2 weeks during the subsequent 4 weeks. We measured the Clinical Inflammatory Bowel Disease Activity Index (CIBDAI), Canine Chronic Enteropathy Activity Index (CCECAI), serum albumin concentration, and prednisolone dosage in each dog 30 days before treatment, immediately before treatment, and at 2 weeks, 1 month, and 2 months after the start of treatment. The primary endpoint of the treatment response was clinical remission based on the percentage reduction in CIBDAI and CCECAI at the last follow-up.<h4>Results</h4>Sixteen dogs with refractory CIE were included in the study. Repeated intravenous infusions of allogeneic adipose-derived MSCs improved the CIBDAI, CCECAI, and serum albumin concentrations over time in dogs with refractory CIE, with nine of 16 dogs (56%) achieving clinical remission and two dogs (13%) partial remission. Throughout the study, no dogs exhibited acute adverse reactions or significant increases in inflammatory markers during or after the cell infusions. Dogs that responded to canine adipose-derived MSC therapy had significantly lower serum albumin concentrations and a higher prevalence of hypoalbuminemia and lacteal dilatation.<h4>Conclusions</h4>Repeated intravenous infusions of allogeneic adipose-derived MSCs led to a clinical improvement in some dogs with refractory CIE without marked acute adverse events. Our results suggest that MSC therapy is particularly effective for CIE dogs with hypoalbuminemia.