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Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres
Published on: November 5, 2016
beta-Cell specific cytoprotection by prolactin on human islets
T Yamamoto1, C Ricordi, A Mita
1Diabetes Research Institute, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida 33136, USA.
Prolactin (PRL) supplementation enhances beta-cell viability and survival in human islets cultured in vitro. This finding supports the development of targeted cytoprotective strategies for improved islet transplantation outcomes.
Area of Science:
- Endocrinology
- Cell Biology
- Transplantation Science
Background:
- Cytoprotective agents can improve islet isolation and transplantation.
- Non-selective agents may negatively impact beta-cell function and survival.
- Beta-cell-selective protection is needed for enhanced islet transplantation outcomes.
Purpose of the Study:
- To investigate the beta-cell-selective cytoprotective effects of prolactin (PRL) on human islet viability and function.
- To determine if PRL supplementation in culture medium improves islet preparation quality.
Main Methods:
- Human islets were cultured with or without recombinant human PRL (500 microg/L) for 48 hours.
- Flow cytometry and Laser Scanning Cytometry (LSC) assessed fractional viability and cellular composition.
- Islet potency was evaluated in vivo via transplantation into diabetic immunodeficient mice.
Main Results:
- PRL treatment increased relative viable beta-cell mass by 28% (P = .018) and relative islet beta-cell content by 19% (P = .029).
- All transplanted mice in both PRL and control groups achieved normoglycemia.
- PRL treatment did not alter overall islet function post-transplantation.
Conclusions:
- Prolactin (PRL) enhances beta-cell-specific viability and survival of human islets in vitro.
- PRL demonstrates potential as a beta-cell-selective cytoprotective agent.
- Developing novel beta-cell-specific strategies may significantly improve islet transplantation success.
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