Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb.
Bottom Line: Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB-derived neural stem cells.We also show that adult neural progenitors derived from DB animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of DB animals reduces glucose levels.This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes.
Affiliation: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan. firstname.lastname@example.orgShow MeSH
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Mentions: Adult HPC and OB NSCs were prepared from type I (STZ-induced DB rats) and type II DB rats (GK/slc DB rats) and were transplanted back into the pancreases of type I and type II DB rats, respectively. During 2 weeks ex vivo culture of NSCs, insulin expression was examined following Wnt3a and anti-IGFBP-4 addition. Although the HPC of DB animals contained higher IGFBP-4 and lower Wnt3 levels than wild-type (Fig 2D), Wnt3a and anti-IGFBP-4 treatment during the ex vivo culture rescued insulin expression (Fig 5A). These HPC and OB NPs were infected with a retroviral CAG promoter-driven EGFP expression vector to trace the grafted cells (Zhao et al, 2006). GFP+ NPs were transplanted into the pancreas of 8-week-old DB rats. Three to five collagen sheets were stacked and grafted near the splenic lobe among the three pancreatic lobes (i.e. the splenic, gastric and duodenal lobes, n = 8 per group), and blood glucose levels were recorded. Seventeen weeks after the transplantation, rats were injected with BrdU daily for 10 days.
Affiliation: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan. email@example.com