Saroglitazar Patent

on a selected group. Included in this group was a batch that utilized 2.76109 hESC and yielded 3.36109 Stage-4 cells, as a demonstration of the scalability of this process. Two groups of processes that were performed semiconsecutively, termed ��13C”, were selected to investigate lot-to-lot consistency. Group 1 consisted of: MCB4 expt #1820, RCB-Dw expt #2530; and Group 2 of: MCB4 expt #21, WCB4B expt #3537. Boxplots of the cellular composition of all the manufacturing runs compared to the 13C group, demonstrated a robust and consistent distribution of pancreatic lineages in sequential experiments. A bank comparison confirmed that such consistency was achieved from 6 different CyT49 banks, indicating excellent process control over pancreatic specification. An average of 51.961.5 % immature endocrine or poly-hormonal cells, 31.961.0% PE cells, and 14.461.0% PDX1expressing endoderm were observed, with only 1.860.4% of cells not positively stained for any of these markers. The means within the PE, endocrine, or PDX-1 only groups were not statistically different, whereas the mean of the residual population ZM-447439 site Production of Functional Pancreatic Progenitors 6 Production of Functional Pancreatic Progenitors in the differentiation runs from MCB4 was lower than those from the RCB-D, MCB3, RCB-Dw and WCB4B banks. While highlighting change in only a minor fraction of the population, it suggests that the four MCB4derived differentiation runs exhibited the tightest technical control over target lineage specification. Gene expression analysis of the 13C group by digital mRNA profiling, also highlighted the reproducibility of our system, in particular the consistency of mRNA dynamics between independent experiments. In addition to the expected sequence of target mesendoderm, endoderm, gut and pancreatic lineage marker expression as cells proceed through each successive stage of differentiation, we observed the rapid downregulation of markers of undifferentiated cells, such as OCT4, NANOG, SOX2, DPPA4 and very low expression levels of markers for mesoderm, neural ectoderm, trophectoderm, and intestinal, or PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22189787 liver endoderm phenotypes. The precise dynamics of gene regulation from stage-tostage and from process-to-process confirm tight control of each stage of differentiation. We expect that the elevated level of process control implemented through all phases of scaled hESC culture, aggregation and differentiation contributes to minimizing overall process variation. Reproducibility of Generating Functional Glucoseresponsive, Insulin-secreting Cells in vivo We tested the pancreatic populations generated in thirty-one scaled differentiation runs for the capacity to generate islet-like tissue with functional insulin-secreting cells after implantation into the epididymal fat pad of male SCID/Bg mice. In total, 240 mice were implanted with typically 36106 cells, in 44 cohorts, of which 228 showed evidence of cell engraftment, remained healthy through at least 3 months and exhibited a functional response to glucose challenge. Based on our previous findings, we scored mice with a maximal-stimulated-release of.2000 pM serum human C-peptide as a high-functioning group, 457462415 pM, weeks 2150) which would be fully protected against STZ-induced hyperglycemia. A second group of 62 mice also exhibited glucose-stimulated release of human C-peptide, but did not reach this 2000 pM benchmark by 25 weeks post-engraftment. Such animals would be predicted to be partially prote