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  2. Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation

Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation

  • Biomedicines. 2020 Nov 9;8(11):485. doi: 10.3390/biomedicines8110485.
Paulami Mandal 1 Debojyoti De 2 Dong Uk Im 3 Sung Hee Um 3 Kyeong Kyu Kim 1
Affiliations

Affiliations

  • 1 Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
  • 2 Department of Biotechnology, National Institute of Technology, Durgapur 713209, India.
  • 3 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
Abstract

Diabetes is a concerning health malady worldwide. Islet or pancreas transplantation is the only long-term treatment available; however, the scarcity of transplantable tissues hampers this approach. Therefore, new cell sources and differentiation approaches are required. Apart from the genetic- and small molecule-based approaches, exosomes could induce cellular differentiation by means of their cargo, including miRNA. We developed a chemical-based protocol to differentiate mouse embryonic fibroblasts (MEFs) into β-like cells and employed mouse insulinoma (MIN6)-derived exosomes in the presence or absence of specific small molecules to encourage their differentiation into β-like cells. The differentiated β-like cells were functional and expressed pancreatic genes such as Pdx1, Nkx6.1, and Insulin 1 and 2. We found that the exosome plus small molecule combination differentiated the MEFs most efficiently. Using miRNA-sequencing, we identified miR-127 and miR-709, and found that individually and in combination, the miRNAs differentiated MEFs into β-like cells similar to the exosome treatment. We also confirmed that exocrine cells can be differentiated into β-like cells by exosomes and the exosome-identified miRNAs. A new differentiation approach based on the use of exosome-identified miRNAs could help people afflicted with diabetes.

Keywords

diabetes; differentiation; exocrine cells; exosomes; miRNA; small molecules; β-cell.

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