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Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program

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Reprogramming mouse embryo fibroblasts to functional islets without genetic manipulation.

Bhawna Chandravanshi¹, Ramesh Bhonde¹

¹School of Regenerative Medicine, GKVK Post, Allalasandra, Yelahanka, Bangalore, Karnataka, India.

Journal of Cellular Physiology

|June 29, 2017

Summary

Mouse embryo fibroblast cells can differentiate into insulin-producing islet-like cell aggregates (ICAs). This discovery offers a potential new source for treating type 1 diabetes.

Keywords:

C-peptide dithizone insulin-like cell aggregates mesenchymal stem cells mouse embryo fibroblast

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Generation of Scaffold-free, Three-dimensional Insulin Expressing Pancreatoids from Mouse Pancreatic Progenitors In Vitro

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Published on: June 2, 2018

Area of Science:

Stem Cell Biology
Endocrinology
Regenerative Medicine

Background:

Generating sufficient functional islets is crucial for treating type 1 diabetes.
Mouse embryo fibroblast cells (MEFs) are readily available and possess differentiation potential.

Purpose of the Study:

To investigate the differentiation capacity of MEFs into insulin-producing islet-like cell aggregates (ICAs).
To explore the therapeutic potential of MEF-derived ICAs for diabetes treatment.

Main Methods:

MEFs were isolated and characterized for surface markers and tri-lineage differentiation.
MEFs were cultured in serum-free media with islet differentiating reagents.
Pancreatic lineage gene expression and protein markers (C-peptide, insulin, glucagon, somatostatin) were analyzed.
In vitro glucose stimulation and in vivo transplantation studies were performed.

Main Results:

MEFs expressed mesenchymal stem cell (MSC)-like markers (Sca1, CD44, CD73, CD90) and differentiated into ICAs.
ICAs exhibited positive staining for pancreatic beta-cell markers and functional insulin secretion in response to glucose.
Transplantation of ICAs reversed diabetes in streptozotocin-induced diabetic mice.

Conclusions:

MEFs contain MSC-like cells capable of differentiating into functional, insulin-producing ICAs.
This study provides a novel strategy for generating pancreatic islets from fibroblasts.
MEF-derived ICAs hold promise for the future treatment of type 1 diabetes.