Allogeneic Bone Marrow Cocultured With Human Islets Significantly Improves Islet Survival and Function In Vivo

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Abstract

Background

A significant barrier to islet transplantation is the rapid loss of human islet function in vivo. The present study evaluates whether bone marrow (BM) could be used to support human islet survival and function in vivo.

Methods

We cocultured human islets and BM for 3 weeks before transplantation into the left subrenal capsule of diabetic severe combined immunodeficient mice.

Results

The cocultured human islets before transplantation demonstrated improved viability, increased size, and migration capacity in vitro. After 4 months, animals transplanted with precultured BM/islets exhibited euglycemia and detectable human insulin levels (157 μU/mL), whereas no human insulin was detected in the islet-only transplantation group. Furthermore, the removal of the transplants on day 126 resulted in hyperglycemia, indicating that the reduction of blood glucose was dependent on the transplants. Diabetic mice transplanted with BM/islets demonstrated the longest survival period (130 vs. 40 days for those with islet-only transplants). The transplanted BM/islets showed signs of vascularization and migration from the renal capsule into medulla.

Conclusions

Our results suggest that BM precultured with human islets may enhance the survival and function of transplanted islets, thus significantly improving the therapeutic efficacy of islet transplantation for type 1 diabetes.

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