The potential to one day treat type 1 diabetes using transplants of insulin-producing beta-cells derived from pancreatic progenitors may have just crept a tad closer, if findings by a group of researchers at the University of California, San Diego (UCSD) can be verified. The team has identified a cell surface marker on a subpopulation of cells in the pancreas that appears to identify them as pancreatic stem cells (PnSCs), a cell type which has never actually been firmly demonstrated in human or animal tissues.
Current approaches to cell replacement therapy for diabetes involves the transplantation of pancreatic islets, which involves numerous transplant procedures. Although it is feasibly possible to derive insulin-producing cells from either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), there are technical issues which have yet to be solved. What is ideally needed is a source of stem cells derived directly from the pancreas that can readily be prompted to differentiate into the desired cell type.
Research by Alberto Hayek, Ph.D., and colleagues now indicates that human pancreatic ductal cells that express the cell surface stem cell marker stage-specific embryonic antigen 4 (SSEA4) may represent this elusive population of PnSCs that has long been postulated but never quite isolated. The cells, located in the exocrine portion of the adult human pancreas but not inside islets themselves, also express ductal, pancreatic progenitor, and stem cell protein markers. Interestingly, the investigators found that SSEA4-expressing cells isolated from fetal pancreatic tissue additionally express a recognized marker of endocrine progenitor cells.
Notably, when the UCSDF team then isolated adult human pancreatic SSEA4+ cells and cultured them in media containing high levels of glucose and B27 supplements, the cells formed aggregate-like spheres and differentiated readily into pancreatic hormone-expressing cells.
“Accumulated evidence supports the concept that pancreatic stem/progenitor cells may originate in the pancreatic duct, where they reside in a quiescent stage,” the authors remark. “We are first to identify SSEA4+ cells in the adult human pancreas with characteristics of pancreatic progenitors. Further clonal analysis would confirm their stemness.... The discovery of specific markers for the identification and purification of human PnSCs would greatly facilitate studies aimed at the expansion of these cells and the development of targeting tools for their potential induction to insulin-producing cells.
Dr. Hayek et al., report on their findings in BioResearch Open Access, in a paper titled "Is stage-specific embryonic antigen 4 a marker for human ductal/stem/progenitor cells?"