cell replacement therapy - Diabetes Research Connection

Diabetes Research News
June 19, 2020

Targeting Stem Cell-Generated Beta Cells for Type 1 Diabetes Treatment

In developing more effective treatment methods for type 1 diabetes, several approaches have targeted the disease at a cellular level. Scientists know that, on the most basic level, the disease stems from the destruction of insulin-producing beta cells. However, they are unsure exactly what causes the body to mistakenly attack and destroy these cells. There have been many studies looking at how to reintroduce or stimulate these beta cells within the body in order to produce insulin naturally, but this is a difficult process and one that is hard to sustain.

A recent study may have found a way to improve the number and quality of beta cells produced for cell replacement therapy. The differentiation of human pluripotent stem cells into targeted beta cells is a long, complex process that can take weeks. Even after the process is finished, there is an assortment of cells that have been produced because not all cells differentiate as desired. In addition, not all beta cells are fully functional.

Researchers found that by adding CD77, a monoclonal antibody, they can better control the differentiation of cells into specific pancreatic progenitors. Having these pancreatic progenitors present at the start of the differentiation process may lead to higher quality beta cells that are more responsive to glucose and have improved insulin secretion abilities. In addition, it may help direct differentiation meaning a more homogenous group of cells is created, which is beneficial for cell replacement therapy. Having more of the desired type of cell can also save time and money.

Being able to better control the differentiation process may improve beta cell replacement therapy options for individuals with type 1 diabetes. Developing ways for the body to once again generate its own insulin and manage blood glucose levels could change the way the disease is managed. This study was a partnership between Helmholtz Zentrum München, the German Center for Diabetes Research (DZD), Technical University of Munich (TUM), and Miltenyi Biotec.

Though not involved with this study, the Diabetes Research Connection stays abreast of the latest advancements in the field and how emerging research may impact the diagnosis, treatment, and management of type 1 diabetes, as well as the search for a cure. As more about the disease is understood, researchers can build on this information. The DRC provides critical funding for early-career scientists whose research is focused on type 1 diabetes. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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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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Diabetes Research News
December 16, 2019

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. Click to learn more about current projects and provide support.

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