Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386864314> ?p ?o ?g. }
Showing items 1 to 67 of
67
with 100 items per page.
- W4386864314 abstract "The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine but it remains an important challenge as it requires the decoupling of the mechanisms supporting progenitor self-renewal and expansion from feed-forward mechanisms promoting their differentiation. The expansion of human pluripotent stem (hPS) cell derived pancreatic progenitors (PP) will accelerate the development of novel therapies for diabetes.We obtained mechanistic insights into the expansion requirements of PP cells and leveraged them to conduct a hypothesis-driven iterative search to identify conditions for the robust and unlimited expansion of hPS cell derived PP cells under GMP-compliant conditions. We show that the combined stimulation of specific mitogenic pathways, suppression of retinoic acid signaling and inhibition of selected branches of the TGFβ and Wnt signaling pathways are necessary for the effective decoupling of PP proliferation from differentiation. This enabled the selection of PDX1+/SOX9+/NKX6.1+ PP cells and their consistent, 2000-fold, expansion over ten passages and 40-45 days. Transcriptome analyses confirmed the stabilisation of PP identity and the effective suppression of differentiation. Using these conditions, PDX1+/SOX9+/NKX6.1+ PP cells, derived from different, both XY and XX, hPS cells lines, were enriched to nearly 90% homogeneity and expanded with very similar kinetics and efficiency. Furthermore, non-expanded and expanded PP cells, from different hPS cell lines, were differentiated in micropatterned wells into homogeneous islet-like clusters (SC-islets) with very similar efficiency. These clusters contained abundant β-cells of comparable functionality as assessed by glucose-stimulated insulin secretion assays.These findings established the signaling requirements to decouple PP proliferation from differentiation and allowed the consistent expansion of hPS cell derived PP cells. They will enable the establishment of large banks of PP cells derived under GMP conditions from diverse hPS cell lines. This will also streamline the generation of SC-islet clusters for further development of the differentiation process, diabetes research, personalized medicine and cell therapies." @default.
- W4386864314 created "2023-09-20" @default.
- W4386864314 creator A5014242783 @default.
- W4386864314 date "2023-09-19" @default.
- W4386864314 modified "2023-09-27" @default.
- W4386864314 title "eLife assessment: Regulation of multiple signaling pathways promotes the consistent expansion of human pancreatic progenitors in defined conditions" @default.
- W4386864314 doi "https://doi.org/10.7554/elife.89962.1.sa0" @default.
- W4386864314 hasPublicationYear "2023" @default.
- W4386864314 type Work @default.
- W4386864314 citedByCount "0" @default.
- W4386864314 crossrefType "peer-review" @default.
- W4386864314 hasAuthorship W4386864314A5014242783 @default.
- W4386864314 hasBestOaLocation W43868643141 @default.
- W4386864314 hasConcept C104317684 @default.
- W4386864314 hasConcept C107459253 @default.
- W4386864314 hasConcept C10854531 @default.
- W4386864314 hasConcept C134018914 @default.
- W4386864314 hasConcept C137620995 @default.
- W4386864314 hasConcept C145103041 @default.
- W4386864314 hasConcept C148738053 @default.
- W4386864314 hasConcept C150194340 @default.
- W4386864314 hasConcept C15729860 @default.
- W4386864314 hasConcept C162317418 @default.
- W4386864314 hasConcept C165220095 @default.
- W4386864314 hasConcept C201750760 @default.
- W4386864314 hasConcept C2779050171 @default.
- W4386864314 hasConcept C2779306644 @default.
- W4386864314 hasConcept C28328180 @default.
- W4386864314 hasConcept C54355233 @default.
- W4386864314 hasConcept C62478195 @default.
- W4386864314 hasConcept C86803240 @default.
- W4386864314 hasConcept C95444343 @default.
- W4386864314 hasConceptScore W4386864314C104317684 @default.
- W4386864314 hasConceptScore W4386864314C107459253 @default.
- W4386864314 hasConceptScore W4386864314C10854531 @default.
- W4386864314 hasConceptScore W4386864314C134018914 @default.
- W4386864314 hasConceptScore W4386864314C137620995 @default.
- W4386864314 hasConceptScore W4386864314C145103041 @default.
- W4386864314 hasConceptScore W4386864314C148738053 @default.
- W4386864314 hasConceptScore W4386864314C150194340 @default.
- W4386864314 hasConceptScore W4386864314C15729860 @default.
- W4386864314 hasConceptScore W4386864314C162317418 @default.
- W4386864314 hasConceptScore W4386864314C165220095 @default.
- W4386864314 hasConceptScore W4386864314C201750760 @default.
- W4386864314 hasConceptScore W4386864314C2779050171 @default.
- W4386864314 hasConceptScore W4386864314C2779306644 @default.
- W4386864314 hasConceptScore W4386864314C28328180 @default.
- W4386864314 hasConceptScore W4386864314C54355233 @default.
- W4386864314 hasConceptScore W4386864314C62478195 @default.
- W4386864314 hasConceptScore W4386864314C86803240 @default.
- W4386864314 hasConceptScore W4386864314C95444343 @default.
- W4386864314 hasLocation W43868643141 @default.
- W4386864314 hasOpenAccess W4386864314 @default.
- W4386864314 hasPrimaryLocation W43868643141 @default.
- W4386864314 hasRelatedWork W1537651933 @default.
- W4386864314 hasRelatedWork W2033967678 @default.
- W4386864314 hasRelatedWork W2063844758 @default.
- W4386864314 hasRelatedWork W2088698936 @default.
- W4386864314 hasRelatedWork W2114014281 @default.
- W4386864314 hasRelatedWork W2300366807 @default.
- W4386864314 hasRelatedWork W2408727903 @default.
- W4386864314 hasRelatedWork W3086620859 @default.
- W4386864314 hasRelatedWork W4378084642 @default.
- W4386864314 hasRelatedWork W162780947 @default.
- W4386864314 isParatext "false" @default.
- W4386864314 isRetracted "false" @default.
- W4386864314 workType "peer-review" @default.