Functional Validation of Human Multipotent Stromal Cell-secreted Islet Regenerative Proteins
Abstract
Diabetes affects ~537 million people worldwide. Although insulin can help manage blood glucose, 80% of patients suffer severe complications, prompting a need for novel therapies. Human bone marrow-derived multipotent stromal cells (MSC) expanded under Wnt-pathway stimulation secrete islet regenerative factors into conditioned media (Wnt+ CM). Proteomic analyses identified 8 secreted proteins (FAM3C, PSAP, SOD1, PPIA, GAL1, CTSB, TGM2, CALU) as top candidates; however, the islet regenerative functions of these proteins have not yet been functionally validated. We tested the islet regenerative capacity of these MSC-secreted proteins in vitro using human islet cultures and in vivo using streptozotocin-treated mice. Although the proteins had minimal effects on islet viability and proliferation in vitro, intrapancreatic injection of the 8-protein combination showed islet regenerative effects comparable to Wnt+ CM in vivo, including decreased hyperglycemia, improved glucose tolerance, and increased beta cell mass. This study provides proof-of-concept for the development of protein-based therapies for diabetes.