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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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Oh JE,Choi OK,Park HS,Jung HS,Ryu SJ,Lee YD,Lee SA,Chung SS,Choi EY,Lee DS,Gho YS,Lee H,Park KS

doi

10.1038/s41598-019-41823-9

subject

Has Abstract

pub_date

2019-03-29 00:00:00

pages

5343

issue

1

issn

2045-2322

pii

10.1038/s41598-019-41823-9

journal_volume

9

pub_type

杂志文章

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