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Sci Rep. 2019 Mar 29;9(1):5343. doi: 10.1038/s41598-019-41823-9.

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

Author information

1
Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
2
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 03080, Republic of Korea.
3
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
4
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
5
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, Republic of Korea.
6
Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea. ehakmo@gmail.com.
7
Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, 05368, Republic of Korea. ehakmo@gmail.com.
8
Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea. kspark@snu.ac.kr.
9
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 03080, Republic of Korea. kspark@snu.ac.kr.
10
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. kspark@snu.ac.kr.

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.

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