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Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic ?-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 ?-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 ?-cells. In vitro primed BMNCs expressed the ?-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.

SUBMITTER: Oh JE 

PROVIDER: S-EPMC6441031 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Oh Ju Eun JE   Choi Ok Kyung OK   Park Ho Seon HS   Jung Hye Seung HS   Ryu Su Jeong SJ   Lee Yong Deok YD   Lee Seung-Ah SA   Chung Sung Soo SS   Choi Eun Young EY   Lee Dong-Sup DS   Gho Yong Song YS   Lee Hakmo H   Park Kyong Soo KS  

Scientific reports 20190329 1


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 di  ...[more]

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