(F1258) CHARACTERISTICS OF MESENCHYMAL STEM CELL THERAPEUTICS CULTURED IN 3D USING GELATIN HYDROGEL SCAFFOLDS AND THEIR EFFICACY IN REFRACTORY INTESTINAL INFLAMMATION
Professor Sapporo Medical University Sapporo, Hokkaido, Japan
Abstract: In inflammatory bowel disease (IBD), refractory erosions and multiple ulcers form in the gastrointestinal tract. Surgical intervention is often performed for complications such as strictures associated with refractory ulcers and complex fistulas. However, these procedures are not curative. Challenges include short bowel syndrome caused by repeated intestinal resections, reduced quality of life (QOL) due to long-term drainage tubes placement, and the potential development of malignancies. Moreover, current immunomodulatory agents are administered systemically, raising concerns about side effects from prolonged use. Therefore, there is an urgent need to develop novel therapies that provide localized, high-efficacy treatment for severe lesions. Mesenchymal stem cells (MSCs) secrete a variety of humoral factors and extracellular vesicles, demonstrating immunomodulatory and tissue repair capabilities. Studies have shown that 3D culturing of MSCs suppresses replicative senescence, prolongs cell viability, and enhances functional properties such as anti-inflammatory effects. However, MSC characteristics vary depending on the culture method. Gelatin hydrogel, which mimics the extracellular matrix in vivo, promotes the proliferation and intercellular interactions of co-cultured cells. It also facilitates the diffusion of nutrients and oxygen essential for cell survival and exhibits excellent biocompatibility. In this study, we developed 3D-cultured MSCs using gelatin hydrogel particles as scaffolds (Gel-MSCs) and evaluated their potential as mucosal-localized therapeutics. We also investigated their characteristics using umbilical cord-derived MSCs and adipose tissue-derived MSCs. Compared to 2D-cultured MSCs (2D-MSCs), Gel-MSCs exhibited enhanced expression of immunomodulatory and tissue repair-related factors, along with increased secretion of prostaglandin E2 (PGE2), which promotes intestinal epithelial regeneration and the regulates intestinal inflammation. Additionally, local administration of Gel-MSCs to severe ulcers in a TNBS-induced colitis rat model enhanced epithelial regeneration and improved MSC retention in mucosal tissues. This report discusses the mechanisms underlying the therapeutic efficacy of Gel-MSCs.
Funding Source: Grants-in-Aid for Scientific Research in Japan SHIBUYA CORPORATION
