Preventing the onset of diabetes with precision delivery of mesenchymal stem cells to the pancreas in a preclinical model

Abstract Background Mesenchymal stem cells (MSCs) represent a promising regenerative therapy associated with anti-inflammatory, anti-apoptotic, and pro-proliferative properties. Despite their significant potential for treating diabetes, the clinical application of MSCs has been hindered mainly due to the low number of intravenously (IV) injected cells that successfully reach the pancreas. Methods In this study, we assessed the protective potential of adipose tissue-derived MSCs (AD-MSCs) in preventing the development of diabetes using a streptozotocin (STZ)-induced diabetic rat model. AD-MSCs were administered 4 h after STZ either via conventional IV injection or through direct intra-arterial (IA) administration into the pancreas. Healthy (no STZ, no MSCs) and diabetic (STZ, no MSCs) control groups were also included. Results Our proof-of-concept data indicate that IA administration of AD-MSCs allowed rats to maintain glycemic control and respond appropriately to glucose challenges following STZ treatment, comparable to healthy controls. In contrast, rats receiving IV AD-MSCs developed hyperglycemia and failed to respond adequately to glucose challenges. In vitro studies demonstrated that AD-MSCs can enhance the viability and function (i.e. insulin secretion) of injured islets. Conclusion Local IA delivery of AD-MSCs into the pancreatic circulation effectively prevents the onset of diabetes in a preclinical rat model, highlighting the need for considering delivery techniques to ensure MSCs can reach their targets in vivo.