Diabetes is an insulin insufficiency disease that affects over 6% of the U.S. population. People with diabetes are at higher risk for heart disease, blindness, kidney failure, and other chronic conditions. Diabetes cost the United States an estimated $132 billion in 2002 in direct medical and indirect expenditures (Hogan et al., 2003). Pancreatic ^-cell death directly leads to Type I diabetes, causing a misregulation of glucose homeostasis. Patients with Type I, insulin-dependent diabetes require exogenous insulin therapy to regulate glucose levels. Neogenesis of ^-cells could lead to an important mechanism of islet cell repopulation and restoration of normoglycemia. Two strategies for producing human islet cells have made significant advances in the past few years: the transformation of pancreatic cells into new islet cells and the isolation and development of stem cells into insulin-producing islet cells. Acquiring renewable sources of cells, either from embryonic or adult stem cells, may overcome problems related to obtaining sufficient numbers of islets for transplant. Specifically, stem cells of the spleen, an organ previously not thought to harbor pancreatic stem cells, have been demonstrated to mature into fully functional islet cells (Kodama et al., 2003). Islet replacement, via adult and embryonic stem cells, represents a promising cure for diabetes.
Regeneration of islet cells for the treatment of diabetes
Although the onset and progression of Type I diabetes can be managed through intensive insulin therapy, this type of therapy does not liberate the patient from insulin dependence. Restoring ^-cell function through regenerating ^-cells from islet cell precursors is an attractive alternative to transplantation of exogenous ^-cells. Problems with scarcity of material and immunological rejection are circumvented by the use of embryonic stem (ES) cells, which can differentiate into a variety of cell lineages in vitro. Soria et al. made use of a cell-trapping system to generate an insulin-secreting cell clone from undifferentiated ES cells (Soria et al., 2000). ES-implanted animals reached a normalized weight by four weeks postimplantation, and implantation led to correction of hyperglycemia within one week. ES-derived insulin-containing cells are able to normalize blood glucose in diabetic mice, but using this technology in human therapies involves first solving problems with ES cell use, including overcoming political obstacles and potential tumor development.
Kodama et al. identified endogenous adult precursor cells of the spleen that can reconstitute functional islets and restore normoglycemia in the pancreas (Kodoma et al., 2003). By utilizing flow cytometry sorting against CD45, a surface marker absent on precursor cells, treatment of prediabetic mice with splenic precursor cells prevents diabetic onset, whereas their untreated littermates became diabetic. The donor precursor spleno-cytes contributed to de novo islet regeneration and rescue of damaged islets. These findings implicate the endogenous adult population of stem cells in therapies to reverse diabetes without the ethical issues associated with the use of ES cells.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...