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Improving Vascularization of Transplanted Islet Cells

One option that researchers have explored for treating type 1 diabetes is cell transplantation. By introducing new pancreatic islet cells, they aim to better control glucose levels and insulin production. However, there are still many challenges surrounding this approach including cell death due to poor vascularization.

Pancreatic islet cells are highly vascularized in order to quickly and easily transport insulin. If they are not able to establish blood vessel connections following transplantation, they cannot work as effectively and may not survive long-term. A recent study has found an improved method for promoting vascularization and enabling more effective cell transplantation.

A multidisciplinary team of researchers developed a biomimetic microvascular mesh that maintained its shape and promoted the survival of transplanted cells by stimulating revascularization. When transplanted into diabetic mouse models, they were able to maintain normoglycemia for up to three months.

The researchers created micropillars to improve anchoring of the microvascular mesh and decrease risk of shrinkage as cells matured. They had success using both human umbilical vein endothelial cells (HUVECs) and human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) in the meshes. Compared to a mesh without these cells, the mesh with the cells showed both anastomoses and vascular remodeling which are essential in vascularization during cell replacement therapy.

Though they have only been tested in mouse models, biomimetic microvascular mesh could one day be used to improve cell replacement therapy for humans with type 1 diabetes in order to improve glycemic control. This study opens doors for additional research and further refining islet transplantation methods.

Though not involved with this study, Diabetes Research Connection (DRC) supports novel research projects that strive to advance treatment for type 1 diabetes and one day find a cure. Early career scientists can receive up to $75K in funding from donations by individuals, corporations, and foundations to support their research. Learn more by visiting http://diabetesresearchconnection.org.

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Antibody-Drug Conjugate May Help Reduce Allograft Rejection.

Cell transplantation has been an area of focus in developing treatment for type 1 diabetes. Many studies have examined both autologous and allogeneic transplants and the benefits and risks they provide. A major challenge continues to be rejection and the body’s destruction of these cells, whether initially derived from its own cells or not.

However, a recent study found that an anti-CD103 antibody-drug conjugate (M290-MC-MMAF) may reduce pancreatic islet allograft rejection in mice. This drug decreased the amount of CD103+CD8+ effector T cells while at the same time increasing the amount of CD4+CD25+ regulatory T cells. This balance led to improved survival rate of the allograft and supported immunosuppression without causing systemic toxicity. When CD103+CD8+ levels were increased, allograft rejection quickly followed.

While this study has only been conducted in mouse models, it shows potential for pancreatic islet allografts in treating type 1 diabetes. Further research is necessary to determine how this process translates to human cells. M290-MC-MMAF could eventually be used as a therapeutic intervention to reduce risk of allograft rejection in humans.

Diabetes Research Connection (DRC), though not involved in this study, stays abreast of the latest discoveries in the field and supports early career scientists in pursuing novel, peer-reviewed research projects related to type 1 diabetes. Scientists receive funding that is critical to conducting research and improving the diagnosis, treatment, and management of the disease and one day finding a cure. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

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