Pancreatic acinar cell reprogramming for beta cell regeneration (FWOAL775)

An inadequate number of insulin-producing beta cells in the pancreas leads to diabetes. Restoration of beta cell number and function by cell transplantation or stimulation of regeneration represents a potential curative therapy. We have shown that exocrine acinar cells, the most abundant cell type in the pancreas, can be converted into functional beta cells in vitro and in vivo by applying extracellular growth factors or cytokines. Further research is required to control this conversion, or cellular reprogramming, and to be able to apply it in an efficient and safe way in humans. We suspect on the basis of our own new findings and those from others, that thyroid hormone signaling represents a powerful regulator of acinar cell plasticity. In this project we want to examine the role of thyroid hormone, its receptor(s) and its intracellular signaling system in the regulation of exocrine acinar cell plasticity and reprogramming into endocrine beta cells. This hormone will be studied in vivo and in vitro, in conjunction with previously reported factors that regulate exocrine-endocrine reprogramming, in rodent and human experimental models. The results of this project could contribute to procure more transplantable insulin-producing cells for cell therapy and in attempting to regenerate beta cells in insulin-dependent diabetes.

Keywords:biomedical sciences

Disciplines:Endocrinology