Development of a scalable method to isolate subsets of stem cell-derived pancreatic islet cells.
Stem Cell Reports
; 17(4): 979-992, 2022 04 12.
Article
em En
| MEDLINE
| ID: mdl-35245441
Cell replacement therapy using ß cells derived from stem cells is a promising alternative to conventional diabetes treatment options. Although current differentiation methods produce glucose-responsive ß cells, they can also yield populations of undesired endocrine progenitors and other proliferating cell types that might interfere with long-term islet function and safety of transplanted cells. Here, we describe the generation of an array of monoclonal antibodies against cell surface markers that selectively label stem cell-derived islet cells. A high-throughput screen identified promising candidates, including three clones that mark a high proportion of endocrine cells in differentiated cultures. A scalable magnetic sorting method was developed to enrich for human pluripotent stem cell (hPSC)-derived islet cells using these three antibodies, leading to the formation of islet-like clusters with improved glucose-stimulated insulin secretion and reduced growth upon transplantation. This strategy should facilitate large-scale production of functional islet clusters from stem cells for disease modeling and cell replacement therapy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Células-Tronco Pluripotentes
/
Células Secretoras de Insulina
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article