A recent study produced the surprising result that insulin gene expression is upregulated in multiple extrapancreatic tissues in conditions of hypergly-caemia, and bone marrow appears to be the major source of these proinsulin-expressing cells, thus highlighting the potential of extra-pancreatic cell sources in the treatment of diabetes. Following bone marrow transplantation and STZ-induced hyperglycaemia in mice, proinsulin and insulinpositive cells were present in the liver, adipose tissue, spleen, bone marrow and thymus, and many of these cells produced glucagon, somatostatin and C-peptide.66
Up to 23% of bone marrow cells in hyperglycaemic mice were immunoreactive for proinsulin, and up to 90% of proinsulin-immunoreact-ive cells in the liver were of bone marrow origin. This implies that hyperglycaemia induces proinsulin production in a population of bone marrow cells, which then migrate and home to the liver, although it is also possible that bone marrow cells migrate to the liver in hyperglycaemic conditions, and subsequently acquire the capacity for proinsulin production.
Interestingly, bone marrow-derived, proinsulin-positive cells were observed, albeit rarely, in the acini of the hyperglycaemic pancreas, but were not found in the islets.66 It is possible that these cells may be the so-called non-haematopoietic tissue committed stem cells (TCSC), identified within the murine bone marrow by Kucia et al.,61 which are released into the peripheral blood following tissue injury and contribute to regeneration in multiple tissues.
Transplantation of fresh, unprocessed wild type adult splenocytes into diabetic NOD mice imposes normoglycaemia and induces long-term disease elimination. Donor-derived islet and pancreatic duct cells were observed, and interestingly, no islets composed entirely of cells of host origin were seen, and pancreatic ducts that were purely of host origin were never seen adjacent to islets containing donor cells. The donor-derived cells contained a normal chromosomal complement and were morphologically normal, suggesting that these cells are formed by splenocyte differentiation and not by fusion of a transplanted cell with an indigenous pancreatic cell.68
Was this article helpful?