The Use of Potent Populations of Expanded Fetal Human Placental Stromal Cells for the Treatment of Dextran-Sodium-Sulfate Induced Colitis in a Mouse Model

Inflammatory Bowel Diseas21e (IBD) is a multifactorial gastrointestinal condition that encompasses two major forms of intestinal inflammation: Crohn's disease (CD) and ulcerative colitis (UC). Both conditions are linked to auto-inflammatory reactions and genetic predispositions, Various drug therapies and biological treatments proposed to reduce IBD associated inflammation. We induced IBD in a mouse model by stimulating bowel inflammation with oral dextran sodium sulfate (DSS) beverage. Our novel cell therapy approach for IBD involves intramuscular (IM) and intraperitoneal (IP) delivery of non-matched, expanded, potent xenogeneic fetal human mesenchymal stromal cells (f-hPSCs) in 2 × 10⁶ cell injections. This cell therapy has already shown previously to induce pro-regenerative and anti-inflammatory effects in different systemic and local disorders. In the current study, IP-injected f-hPSCs, following DSS-induced IBD, enhanced the regenerative processes of the damaged bowel and reduced inflammation, leading to rapid weight regain and decreased inflammation-associated parameters, such as colon edema, bowel shortening, and a threefold increase in bowel mass. Although both IP and IM delivery of f-hPSCs were effective, IP injections produced a superior response. The f-hPSCs injected mice lost only ~15% of their weight at the peak of the IBD damage, compared to ~25% in untreated mice. A reduction in the inflammatory response of the gut was observed, evidenced by a decrease in neutrophil infiltration as measured by a myeloperoxidase (MPO) assay. Additionally, a significant improvement in the histological score of the gut and faster recovery to 90% of its original size were recorded. These findings suggest that f-hPSCs treatments could serve as an effective and safe anti-inflammatory and pro-regenerative treatment for IBD.