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Can Human Cells Be Reprogrammed to Act as Pancreatic Beta Cells?

New technique may lead to novel treatment options for type 1 diabetes patients.

A key feature of type 1 diabetes is an autoimmune response against pancreatic beta cells. The destruction of these beta cells disrupts all aspects of insulin production. At present, treatment for type 1 diabetes revolves around injection of manufactured insulin to replace the insulin lost by beta cell destruction. However, scientists have recently proven that certain cells may be reprogrammed to act as replacement beta cells. There is enormous potential for this treatment approach to improve quality of life by potentially replacing exogenous insulin administration.

The researchers of this study, from the Universite Catholique de Louvain, have shown that human pancreatic duct-derived cells (HDCCs) can be reprogrammed to act as pancreatic beta cells. HDCCs are progenitor cells which can mature into different types of cells depending on different factors in the body.

This new research showed that reprogrammed HDCCs can actually respond to glucose and produce insulin. This was accomplished without direct genetic modification of DNA. Instead, the mRNA of MAFA (a transcription factor) was injected into the cells, where it was converted into a protein that modified the DNA in the HDCCs. This method avoids risks common to stem cell use, such as cancer resulting from uncontrolled propagation.

The modification led to upregulation of genes that code for beta-cell functions. The reprogrammed cells secreted insulin in the pancreas. They stained positive for insulin proteins. The authors of the study indicate that future research is necessary in order to demonstrate that these modified cells can appropriately react to serum glucose levels to secrete the appropriate amount of insulin.

Practice Pearls:

  • Human pancreatic duct-derived cells (HDCCs) are progenitor cells that have previously demonstrated potential to be reprogrammed as beta cells.
  • Using mRNA of the transcription MAFA, HDCCs were successfully reprogrammed to become beta-cell like. This method avoids problems associated with direct genetic modification.
  • More research is necessary to validate the viability of these cells in secreting insulin appropriately in response to glucose.

Corritore E, Dugnani E, Pasquale V, et al. RNA-based MAFA over-expression is sufficient to drive human pancreatic duct-derived cells toward a b-cell-like phenotype. Presented at the 54th Annual European Society for Pediatric Endocrinology Meeting in Barcelona, Spain, October 2015.