nPOD. Beta Cell Development, Differentiation & Regeneration

Identification of novel monoclonal antibodies directed against pancreatic endocrine cell types for in vitroand in vivo analysis and targeting

Diabetes mellitus is a multifactorial disease characterized by progressive loss or dysfunction of the insulin-producing beta cells in the pancreas that leads to chronic hyperglycemia, systemic metabolic complications and multi-organ damages. Nowadays, no current treatments can stop or reverse the disease progression, apart bariatric surgery and human islet transplantation. Therefore, intensive efforts in the field of diabetes research are put into the development of novel therapeutic approaches.Regeneration of β-cells or replacement by β-like cells derived from stem cells hold great promise to stop or reverse disease progression. Unfortunately, the development of new treatment options is limited by our poor understanding of human pancreas organogenesis. The differentiation programs of all islet cells and the way in which islets are formed during pancreas development in their body niche, need to be fully understood1-3.Recently, many promising discoveries that could potentially lead to stem cell-derived functional human islets were made. However, the field currently still lacks of specific tools that can allow for enriching the endocrine progenitors during the differentiation process to improve efficiency and functionality. To date, there is only one beta cell marker available, which is already limited in that it doesn’t mark all beta cells and in early stages of life is not specific for beta cells4. To fill in those gaps, in a screen to identify novel monoclonal antibodies (mAbs) that can be used to isolate and/or target human pancreatic cells, we have identified several mAbs that specifically identify pancreatic endocrine, exocrine and endothelialcells. The mAbs produced have a great potential as: 1) tools to isolate pancreatic cells types and their different subtypes for in-depth characterization of pancreas organogenesis 2) markers to characterize pancreatic cell heterogeneity during diabetes progression 3) novel biomarkers of diabetes 4) as a method to enrich for endocrine progenitors during human stem cell differentiation for cell therapy 5) specific carriers for drug delivery or direct therapeutic tools.

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