STEM CELL THERAPY FOR DIABETES MELLITUS

BY BELSY BOBAN,

PHARM D INTERN, AL SHIFA COLLEGE OF PHARMACY.

Curative therapy for diabetes mellitus mainly implies replacement of functional insulin-producing pancreatic cells, with pancreas or islet-cell transplants. However, shortage of donor organs spurs research into alternative means of generating _ cells from islet expansion, encapsulated islet xenografts, human islet cell-lines, and stem cells. Stem cell therapy here implies the replacement of diseased or lost cells from progeny of pluripotent or multipotent cells. Both embryonic stem cells (derived from the inner cell mass of a blastocyst) and adult stem cells (found in the postnatal organism) have been used to generate surrogate _ cells or otherwise restore-cell functioning. These cells express insulin and genetic markers of _ cells. In culture, the cells secrete insulin in response to glucose, and show intracellular calcium fluctuations similar to normal cells. However, only about 1–3% of the islet cells originate from the transplanted marrow. Direct expansion of beta cells in vitro for use in transplantation (limited proliferative potential of fully differentiated beta cells). Genetic manipulation of an unrelated cell type to secrete insulin in a glucose responsive manner (difficult, to accurately mimic the complex regulatory circuits of a beta cell). Expansion and subsequent differentiation of stem or progenitor cells occur. The proliferative capacity of beta cells in vivo is limited and that new beta cells are mainly generated via their differentiation from undifferentiated progenitor cells. The formation of new islet tissue via the differentiation of stem/progenitor cells in adult pancreas is referred to as islet neogenesis. The first specific progenitor cells for the pancreas are characterized by the expression of the transcription factor Pdx-1. Pdx-1 is expressed early in development (embryonic day 8.5 in the mouse) and its expression is required for the initial pancreatic anlage to bud from the endodermal epithelium. Cell fusion has been suggested as a mechanism of apparent adaption of bone-marrow-derived cells into an extra medullary phenotype. The last finding was made recently by Andreas Lechner and colleagues. One group reports the generation of insulin-producing cells in liver, adipose tissue, spleen, and bone marrow in rodent models of diabetes mellitus. Bone-marrow transplantation shows that most if not all extrapancreatic insulin-producing cells derive from donor bone-marrow. In human beings, early immunological intervention to stop cell destruction during the development of type 1 diabetes mellitus allows recovery of pancreatic endocrine function.

 

REFERENCE

Mehboob A Hussain, Neil D Theise., Stem-cell therapy for diabetes mellitus. Rapid Review. Lancet 2004; 364: 203–05.