Stem cell researchers report a cell therapy that can regenerate and coax a diabetic pancreas to produce insulin. The researchers from ICMR National Institute for Research in Reproductive Health (NIRRH) in Mumbai say this brightens the prospects of cell therapy as a permanent cure for diabetes.

Diabetes results from the loss of 'beta' cells in the pancreas that make insulin, the hormone which acts to lower blood sugar. Diabetic patients have to take insulin injections lifelong. A cell therapy that can coax the diabetic pancreas to produce insulin has been the dream of stem cell researchers worldwide.

The team led by Deepa Bhartiya found such stem cells in adult mouse pancreas — the Very Small Embryonic-Like cells (VSELs) — spherical in shape and slightly smaller than red blood cells. These cells are 'pluripotent' — meaning they can turn into any other type of cell. These cells available within the pancreas (endogenous) can be manipulated to regenerate the diabetic pancreas in humans in future, their report says.

VSELs exist in all adult tissues and they serve as a backup pool for stem cells. Earlier studies by her team found that VSELs exist in mouse testis as well as in the ovaries. "We report for the first time the existence of VSELs in pancreatic islets (which are clusters containing several types of cells including beta cells)," they report. These stem cells were confirmed to be pluripotent by their expression of nuclear OCT-4 (octamer-binding transcription factor 4) — the most crucial marker for pluripotency — besides other markers.

"Our results are in complete contrast with the current understanding that the pancreas does not harbour stem cells," Bhartiya said. "These cells have not been so far reported in adult tissues as they unknowingly get discarded while processing due to their small size."

Regenerative medicine currently relies on pluripotent stem cells either extracted from a very early stage embryo (ES cells), or from adult cells that have been induced into a pluripotent state (iPS cells). They have not been used much in treatment of diabetes. "The only clinical trial using ES cells to treat diabetes initiated by Viacyte Inc., a California-based company, five years ago has not given any results yet," Bhartiya told Nature India .

"We have, on the other hand, our mouse study shows the presence of stem cells in the pancreatic islets and their ability to generate new insulin producing islet," she said. There should be no concern regarding the scarce nature of VSELs in pancreas since, when the need arises, these stem cells expand and undergo differentiation," she added.

Mariusz Ratajczak at the Stem Cell Institute of the University of Louisville, who first discovered VSELs in adult bone marrow in 2006 said the finding that small sized pluripotent stem cells do exist in adult pancreas has huge translational potential.

Bhartiya admits that while it will be ideal to manipulate these endogenous cells to regenerate the diabetic pancreas, "VSELs are still struggling to get acknowledged widely by the scientific community." She is hopeful this will change.

References

1. Subhan Ali Mohammad et al. Mouse pancreas stem/progenitor cells get augmented by streptozotocin and regenerate Diabetic pancreas after partial pancreatectomy. Stem Cell Rev. Rep. (2019) doi: 10.1007/s12015-019-09919-x