Abstract
In vitro-generation of β-cells from Wharton’s jelly mesenchymal stem cells (WJ-MSCs) could provide a potential basis for diabetes mellitus cell therapy. However, the generation of functional insulin-producing cells (IPCs) from WJ-MSCs remains a challenge. Recently, obestatin, a gut hormone, was found to promote β-cell generation from pancreatic precursor cells. Accordingly, we hypothesize that obestatin can induce the differentiation of WJ-MSCs into IPCs. Therefore, the purpose of the current study is to examine the ability of obestatin to generate IPCs in comparison to well-known extrinsic factors that are commonly used in IPCs differentiation protocols from MSCs, namely exendin-4 and glucagon-like peptide-1 (GLP-1). To achieve our aims, WJ-MSCs were isolated, cultured and characterized by immunophenotyping and adipocytes differentiation. Afterwards, WJ-MSCs were induced to differentiate into IPCs using two differentiation protocols incorporating either exendin-4, GLP-1 or obestatin. The pancreatic progenitor marker, nestin and β-cell differentiation markers were assessed by qRT-PCR, while the functionality of the generated IPCs was assessed by glucose-stimulated insulin secretion (GSIS). Our results showed that WJ-MSCs exhibit all the characteristics of MSCs. Interestingly, using obestatin in both the short and long differentiation protocols managed to induce the expression of β-cell markers, similar to exendin-4. In GSIS, IPCs generated using either GLP-1 or obestatin showed higher secretion of insulin as compared to those generated using exendin-4 under low-glucose conditions but failed to show a significant response to increased glucose. These results indicate obestatin can be considered as a novel potential factor to consider for generation of IPCs from WJ-MSCs.
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Abbreviations
- GLP-1:
-
Glucagon like peptide-1
- GLP-1R:
-
Glucagon-like peptide-1 coupled receptors
- GPR-39:
-
Glucagon like peptide receptor-39
- IPCs:
-
Insulin-producing cells
- iPSCs:
-
induced pluripotent stem cells
- MSCs:
-
Mesenchymal stem cells
- T1DM:
-
Type 1 diabetes mellitus
- WJ:
-
Wharton’s jelly
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This research was partially funded by Ain Shams University, Cairo, Egypt as one of the Applied Researches Grants supported by the University.
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Supplemental Figure 1
Images of cells generated by either short or long differentiation protocols: Short protocol: (a) control cells, (b) exendin-4, (c) GLP-1 and (d)obestatin. Long protocol: (e) control cells, (f) exendin-4, (g) GLP-1 and (h) obestatin. Scale bar = 50 μm. (GIF 476 kb)
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El-Asfar, R.K., Kamal, M.M., Abd EL-Razek, R.S. et al. Obestatin can potentially differentiate Wharton’s jelly mesenchymal stem cells into insulin-producing cells. Cell Tissue Res 372, 91–98 (2018). https://doi.org/10.1007/s00441-017-2725-6
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DOI: https://doi.org/10.1007/s00441-017-2725-6