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Diabetes Research News
February 28, 2020

Improved Beta Cell Function of Transplanted Islet Cells in T1D

One of the major challenges of using transplanted islet cells in the treatment of type 1 diabetes is cell death. Due to cellular stressors, poor oxygenation or vascularization, autoimmune response, and other factors, not all transplanted cells survive, and this can make treatment less effective. The body needs functional insulin-producing islet cells in order to effectively regulate blood sugar levels.

A recent study found that coculturing allogeneic islet beta cells with mesenchymal stromal cells (MSCs) may improve not only cell survival, but function as well. After donor cells are procured, they must be cultured and tested before being transplanted. This can generate significant cellular stress including hypoxia or low oxygenation, which can in turn lead to cell death. However, researchers found that MSCs support islet cells during this culture period by improving oxygenation and insulin secretion.

They also found that in response to these stressors, MSCs actually initiate mitochondria transfer to the islet beta cells. This may improve mitochondrial ATP generation which plays an integral role in controlling insulin secretion. As a result, as glucose levels around the beta cells increased, so did their production and secretion of insulin.

Researchers experimented with this coculturing process with both mouse cells and human cells and found that human cells have a greater response and higher level of MSC-mediated mitochondria transfer that occurs. Though more extensive testing is necessary, these results show that MSCs may be an essential part of clinical islet transplantation and improved efficacy of beta cell function in treating individuals with type 1 diabetes.

Diabetes Research Connection (DRC) is interested to see how this study evolves moving forward and what it may mean for future therapeutic treatments for the disease. The DRC, though not involved in this study, provides critical funding for early career scientists pursuing novel, peer-reviewed research projects for type 1 diabetes. Click to learn more about current projects and provide support.

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Diabetes Research News
January 10, 2020

Unraveling the Process of Fetal Pancreas Development

Cell replacement therapy has been at the forefront of type 1 diabetes research for many years. Researchers have explored different ways to reintroduce insulin-producing beta cells into the pancreas or stimulate the body to begin producing these cells once again. A major challenge is often rejection of the cells by the body, or limited sustainability due to poor vascularization or an autoimmune response.

However, a recent study looks at the function of human multipotent progenitor cells (hMPCs) during development of the pancreas in human fetuses. Scientists were able to safely recover live cells from fetal tissue during the second trimester of development. They found that hMPCs located within the tip of the epithelium contained both SOX9 ad PTF1A transcription factors. However, according to their research, “tip cells did not express insulin, glucagon, or amylase,” which demonstrated their lack of lineage-specific markers. That means that they were uncommitted cells and could potentially differentiate into any of the three major types of pancreatic cells: ductal, endocrine, or acinar.

The proportion of SOX9+/PTF1A+ cells greatly decreased during the second trimester, however. They accounted for more than 60% of cells up to 13.5 weeks of gestation, but after that, there was a significant decrease over the following weeks to less than 20%. During the second trimester, hMPCs also begin the process of branching morphogenesis and divide between tip and truck cells. Truck cells become ductal and endocrine cells, but tip cells become acinar cells.

As researchers gain a deeper understanding of how the pancreas develops and how cell expression and differentiation takes place, they may be able to enhance cell replacement therapy options. According to the study, “This first ‘snapshot’ of the transcriptional network of human pancreatic progenitors opens new avenue in understanding human pancreas development, pancreatic specification and supports our ultimate goal of understanding possible mechanisms for pancreas regeneration.”

Diabetes Research Connection (DRC) is interested to see how this research may influence future treatment options for individuals with type 1 diabetes. By better understanding the pancreas at a cellular level, it could stimulate more advanced therapies. The DRC provides critical funding for novel, peer-reviewed research studies focused on the diagnosis, treatment, and eventual cure for type 1 diabetes. Early career scientists have the opportunity to move forward with their research and contribute to the growing understanding of the disease and treatment options. Learn more and support these efforts by visiting http://diabetesresearchconnection.org.

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