Endocrine Abstracts

Stem cells are clonogenic cells capable of both self-renewal and multilineage differentiation. Therefore, these cells have the potential to proliferate and differentiate into any type of cell and to be genetically modified ‘in vitro’, thus providing cells which can be isolated and used for transplantation. Moreover, these derived cells have proven to be useful in different animal models. Using a combination of several directed differentiation methods (nicotinamide, sonic hedgehog signalling inhibition, soluble factors from pancreatic buds] and a ‘cell trapping’ system, we have obtained insulin-secreting cells from undifferentiated embryonic stem cells. Lineage-trapping constructs used allows the expression of a neomycin selection system under the control of the regulatory regions of insulin gene and other B-cell genes, such as Nkx6.1. Selection of differentiated cells exclude non-differentiated cells which use to be present and are teratogenic. Transplanted animals correct hyperglycaemia within 1 week and restore body weight in four weeks. Graft removal rescued the diabetic condition. Glucose tolerance test (IPGTT) and blood glucose normalization after a challenge meal was similar in control and in transplanted mice. More recently, progenitors from peripheral human blood cells (PCMO) have been convinced to acquire an insulin-producing phenotype which normalize blood glucose of immunocompromised (SCID) diabetic mice, an option with tentative applications in regenerative medicine. This approach opens new possibilities for tissue transplantation in the treatment diabetes mellitus.

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