Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components

Abstract

Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs.

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results

“…Following OCP treatment, we also noted increased expression of several interesting inflammation pathway members. Transforming growth factor-beta 1 (TGFB1) is an antiinflammatory cytokine that has been shown to play a role in endometriosis pathogenesis [47,48] and suppresses or promote endometrial cancer depending on CD73 expression [49]. Its decreased expression after OCPs will require further investigation.…”

Clinical Translational Potentials of Stem Cell-Derived Extracellular Vesicles in Type 1 Diabetes

“…However, Ribeiro et al found that human pancreatic islet-derived EVs improve the differentiation of iPSC cluster culture in 3-D collagen hydrogel with increased pancreatic marker expression (148). Recently, Oh and colleagues showed that b-cell-derived EVs can directly trigger the differentiation of bone marrow mononucleated cells into insulin-producing cells (149). These findings suggest that stem cell-derived EVs may serve as possible mediators for the development of insulin-producing cells from non-beta pancreatic cells.…”