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

Ju Eun Oh, Ok Kyung Choi, Ho Seon Park, Hye Seung Jung, Su Jeong Ryu, Yong Deok Lee, Seung Ah Lee, Sung Soo Chung, Eun Young Choi, Dong Sup Lee, Yong Song Gho, Hakmo Lee, Kyong Soo Park

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5343
Pages (from-to)5343
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 29 Mar 2019

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