Julia C. Lin

Human Pancreatic Islet-Derived Progenitor Cell Engraftment in Immunocompetent Mice

The potential for the use of stem/progenitor cells for the restoration of injured or diseased tissues has garnered much interest recently, establishing a new field of research called regenerative medicine. Attention has been focused on embryonic stem cells derived from human fetal tissues. However, the use of human fetal tissue for research and transplantation is controversial. An alternative is the isolation and utilization of multipotent stem/progenitor cells derived from adult donor tissues. We have previously reported on the isolation, propagation, and partial characterization of a population of stem/progenitor cells isolated from the pancreatic islets of Langerhans of adult human donor pancreata. Here we show that these human adult tissue-derived cells, nestin-positive islet-derived stem/progenitor cells, prepared from human adult pancreata survive engraftment and produce tissue chimerism when transplanted into immunocompetent mice either under the kidney capsule or by systemic injection. These xenografts seem to induce immune tolerance by establishing a mixed chimerism in the mice. We propose that a population of stem/progenitor cells isolated from the islets of the pancreas can cross xenogeneic transplantation immune barriers, induce tissue tolerance, and grow.

Gender-based differences in glycaemic control and hypoglycaemia prevalence in patients with type 2 diabetes: results from patient-level pooled data of six randomized controlled trials.

To determine the impact of gender on glycaemic control and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2DM).

NRSF/REST confers transcriptional repression of the GPR10 gene via a putative NRSE/RE-1 located in the 5' promoter region.

The G protein‐coupled receptor GPR10 is highly localized to areas of the brain. In an effort to reveal transcriptional determinants of this tissue specificity, we recognized a putative NRSE (neuron‐restrictive silencer element) located in the 5′ promoter region of the gene. The cognate NRSE binding protein NRSF (neuron‐restrictive silencer factor) restricts gene expression to mature neurons and endocrine cells by repressing their transcription in non‐neuronal/‐endocrine cells. In cell lines where NRSF‐mediated gene repression has been functionally established, the activity of the GPR10 promoter was repressed in a manner consistent with NRSE‐dependent regulation. A specific point mutation to confer non‐functionality of the NRSE revealed a 10‐fold de‐repression of reporter gene expression. In contrast, in the GPR10‐expressing cell line GH3, mRNA transcripts of NRSF were undetectable and suppression of promoter activity was not observed. However, transfection of a rat NRSF expression vector resulted in significant repression of transcription, which was reversed by mutation of the NRSE. In conclusion, we demonstrate that the GPR10 gene is specifically regulated by NRSF, and suggest this to be a contributory factor in the tissue‐specific distribution of GPR10 in vivo.