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Updated: Jul 19, 2026
Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
Bone Marrow Mesenchymal Stem Cells-Derived miR-21-5p Protects Grafted Islets Against Apoptosis by Targeting PDCD4
Jingwen Wang1, Jiale Wang1, Ying Wang1
1Department of Renal Transplantation, Hospital of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta Western Rd, Xi'an 710061, Shaanxi Province, People's Republic of China.
Abstract:
The apoptosis of grafted islets is an urgent problem due to the high rate of islet loss soon after transplantation. MicroRNA-21-5p (miR-21-5p) is an essential mediator of bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exo) during anti-apoptosis, but its effect and the underlying molecular mechanism in islet transplantation remain partially understood. Here, we found that miR-21-5p could be delivered to islet cells via BMSCs-Exo. Subsequently, we demonstrated that miR-21-5p overexpression reduced apoptosis in islets and INS-1 cells, whereas miR-21-5p inhibition enhanced apoptosis. A mechanistic analysis involving RNA sequencing and bioinformatic analysis was performed to determine the interaction between miR-21-5p and its target gene programmed cell death 4 (PDCD4), which was further verified by a dual luciferase assay. In vivo, the grafted islets overexpressing miR-21-5p showed a higher survival rate, better insulin secretion function, and a lower apoptosis rate. In conclusion, these results demonstrated that miR‑21‑5p from BMSCs-Exo protects against the apoptosis of grafted islets by inhibiting PDCD4 expression. Hence, miR-21-5p can be used as a cell-free therapeutic agent to minimize β-cell apoptosis at the early stage of islet transplantation.
Insights
Bone marrow mesenchymal stem cell-derived exosomes deliver microRNA-21-5p (miR-21-5p) to protect grafted islets from apoptosis by inhibiting programmed cell death 4 (PDCD4). This offers a new cell-free therapy for islet transplantation.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Immunology
Background:
- Islet transplantation is crucial for diabetes treatment but suffers from high graft loss due to apoptosis.
- MicroRNA-21-5p (miR-21-5p) delivered by bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exo) shows anti-apoptotic potential.
- The precise mechanism of miR-21-5p in islet transplantation is not fully elucidated.
Purpose of the Study:
- To investigate the role and mechanism of miR-21-5p from BMSCs-Exo in protecting grafted islets from apoptosis.
- To explore the therapeutic potential of miR-21-5p in islet transplantation.
Main Methods:
- Delivery of miR-21-5p via BMSCs-Exo to islet cells and INS-1 cells.
- Overexpression and inhibition of miR-21-5p to assess apoptosis rates.
- RNA sequencing and bioinformatic analysis to identify target genes.
- Dual luciferase assay to confirm miR-21-5p and target gene interaction.
- In vivo studies using grafted islets with miR-21-5p overexpression.
Main Results:
- miR-21-5p delivered by BMSCs-Exo effectively reduced islet and INS-1 cell apoptosis.
- miR-21-5p directly targets and inhibits programmed cell death 4 (PDCD4) expression.
- Grafted islets overexpressing miR-21-5p exhibited improved survival, insulin secretion, and reduced apoptosis in vivo.
Conclusions:
- miR-21-5p from BMSCs-Exo protects grafted islets against apoptosis by downregulating PDCD4.
- miR-21-5p represents a promising cell-free therapeutic strategy to enhance islet transplantation outcomes by minimizing beta-cell apoptosis.
