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Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous
Gauree S Chendke1,2, Bhushan N Kharbikar2, Sudipta Ashe3
1UC Berkeley - UCSF Graduate Program in Bioengineering San Francisco California USA.
Bioengineering & Translational Medicine
|July 21, 2023
Summary
A new prevascularized implantation method improves beta cell replacement therapy for type 1 diabetes. This approach enhances vascular integration and beta cell function, crucial for managing blood glucose levels.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Endocrinology
Background:
- Type 1 diabetes (T1D) necessitates beta cell replacement therapy (BCRT) to restore glucose regulation.
- Current BCRT faces limitations due to immune rejection and poor engraftment of encapsulated cells.
- Implant hypoxia and nutrient deprivation hinder transplanted beta cell function.
Purpose of the Study:
- To introduce a novel replenishable prevascularized implantation methodology (RPVIM) for BCRT.
- To improve vascular integration and nutrient supply to encapsulated beta cells.
- To enhance the long-term function and survival of transplanted beta cells in T1D patients.
Main Methods:
- Developed and tested the RPVIM for subcutaneous implantation of encapsulation devices.
- Prevascularized empty devices for 14 days before inserting stem cell-derived insulin-producing beta cells.
- Compared RPVIM with standard implantation (SIM) and standard prevascularization (SPVIM) methods.
Main Results:
- Over 75% of RPVIM devices showed signal after 28 days, significantly higher than SIM and SPVIM.
- RPVIM devices demonstrated superior vascular integration and solute transport.
- Encapsulated beta cells within RPVIM devices maintained function, confirmed by glucose tolerance tests and histology.
Conclusions:
- RPVIM offers a promising strategy to overcome engraftment and vascularization challenges in BCRT.
- This methodology supports sustained function of transplanted beta cells, crucial for T1D management.
- RPVIM has the potential to advance the clinical application of beta cell replacement therapy.
