Controlling human stem cell-derived islet composition using magnetic sorting DOI Creative Commons
Alyssa M. Kelley,

Mira Shunkarova,

Marlie M. Maestas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Stem cell-derived islets (SC-islets) consists of multiple hormone-producing cell types and offer a promising therapeutic avenue for treating type 1 diabetes (T1D). Currently, the composition generated within these SC-islets currently cannot be controlled via soluble factors during this differentiation process consist off-target types. In study, we devised magnetic-activated sorting (MACS) protocol to enrich CD49a, marker associated with functional insulin-producing β cells. were from human pluripotent stem cells (hPSCs) using an adherent then sorted aggregated into islet-like clusters produce CD49a-enriched, CD49a-depleted, unsorted SC-islets. Single-cell RNA sequencing (scRNA-seq) immunostaining revealed that CD49a-enriched had higher proportions improved transcriptional identity compared other Functional assays demonstrated exhibited enhanced glucose-stimulated insulin secretion both

Language: Английский

Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell DOI
Jillian Collins, Jessie M. Barra,

Keifer Holcomb

et al.

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(10), P. 6451 - 6466

Published: Sept. 24, 2024

Targeting current therapies to treat or prevent the loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off-target effects. Current efforts target β-cell are limited by a lack β-cell-specific targets inability test multiple targeting moieties with same delivery vehicle. Here, we fabricate tailorable polycaprolactone nanocapsule (NC) which different peptides can be interchangeably attached for delivery. Incorporation cationic surfactant NC shell allows attachment Exendin-4 an antibody ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) targeting. The average size ranges from 250 300 nm polydispersity index under 0.2. NCs nontoxic, stable media culture, lyophilized reconstituted. coated peptide were taken up human cadaveric stem cell-derived β-like cells (sBC) vitro high level specificity. Furthermore, successfully delivered both hydrophobic hydrophilic cargo β-cells. Additionally, Exendin-4-coated targeted mouse vivo. Overall, our have potential improve cell-targeted drug utilized as screening platform cell-targeting peptides.

Language: Английский

Citations

1
Controlling human stem cell-derived islet composition using magnetic sorting DOI Creative Commons
Alyssa M. Kelley,

Mira Shunkarova,

Marlie M. Maestas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Stem cell-derived islets (SC-islets) consists of multiple hormone-producing cell types and offer a promising therapeutic avenue for treating type 1 diabetes (T1D). Currently, the composition generated within these SC-islets currently cannot be controlled via soluble factors during this differentiation process consist off-target types. In study, we devised magnetic-activated sorting (MACS) protocol to enrich CD49a, marker associated with functional insulin-producing β cells. were from human pluripotent stem cells (hPSCs) using an adherent then sorted aggregated into islet-like clusters produce CD49a-enriched, CD49a-depleted, unsorted SC-islets. Single-cell RNA sequencing (scRNA-seq) immunostaining revealed that CD49a-enriched had higher proportions improved transcriptional identity compared other Functional assays demonstrated exhibited enhanced glucose-stimulated insulin secretion both

Language: Английский

Citations

0