V is for Vascularization

V is for Vascularization 

By: Mari Yamamoto

One of the major obstacles that comes with islet transplantation is the re-establishment of the vascular supply. If vascularization is either delayed or insufficient, the transplanted islets won’t survive. Click here for a paper that reviews the various approaches to vascularization, such as extracellular matrix-based scaffolding, pre-vascularization devices and the release of proangiogenic factors. Read on to find out about the recent advances in inducing vascularization to support the survival of islet transplants. 

Stemming the tide of islet death 

  • Mesenchymal stem cells (MSCs) – one study using “Neo-Islets”, generated from islet cells and MSCs, found that their engraftment in NOD mice resulted in long-term glycemic control 
    • This strategy succeeded sans hypoglycemia and without a need for  immunosuppression.
  • Induced pluripotent stem cell-derived endothelial cells – researchers at MIT developed a microbead angiogenesis scaffold to further drive angiogenesis. 
    • Their microbead platform using these iPSC-EC cells have the potential to promote angiogenic sprouting, ultimately supporting vascularization. 

Vascular endothelial growth factor (VEGF) is an important driver of vascularization. Long-standing research administered VEGF in a controlled manner with isolated human and murine islets in a hypoxic environment. The result? Optimized angiogenesis associated with an increase in beta-cell proliferation and mass. 

A paper written last year by Stanford researchers explored pulsed focused ultrasound therapy (pFUS). An attractive non-invasive treatment, the strategy safely stimulated insulin secretion. In vivo, pFUS was able to facilitate islet engraftment and survival by means of islet revascularization and reduction of inflammation. allowed diabetic mice to regain glycemic control. 

A study from Sweden didn’t focus on a specific therapy, but rather the transplantation itself. Researchers compared first islet transplants to the liver done a week apart,. Though the actual mechanisms are unknown, the second transplant turned out to be more successful than the first, as the first transplant caused enhanced engraftment of later transplants. 

The takeaway: Vascularization is important to victory when it comes to islet transplantation. Perhaps combination approaches can enhance vascularization even further? Gaining a fundamental understanding of the vascularization process will be essential for success with islet transplantation.

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