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Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture.
Cuchiara, Maude L; Coskun, Süleyman; Banda, Omar A; Horter, Kelsey L; Hirschi, Karen K; West, Jennifer L.
Afiliación
  • Cuchiara ML; Department of Bioengineering, Rice University, Houston, Texas.
  • Coskun S; Department of Internal Medicine, Yale Cardiovascular Research Center, Vascular Biology and Therapeutics Program and Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut.
  • Banda OA; Departments of Pediatrics and Molecular and Cellular Biology, Children's Nutrition Research Center and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
  • Horter KL; Department of Bioengineering, Rice University, Houston, Texas.
  • Hirschi KK; Department of Bioengineering, Rice University, Houston, Texas.
  • West JL; Department of Internal Medicine, Yale Cardiovascular Research Center, Vascular Biology and Therapeutics Program and Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut.
Biotechnol Bioeng ; 113(4): 870-81, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26497172
ABSTRACT
Hematopoietic stem cells (HSCs) have been used therapeutically for decades, yet their widespread clinical use is hampered by the inability to expand HSCs successfully in vitro. In culture, HSCs rapidly differentiate and lose their ability to self-renew. We hypothesize that by mimicking aspects of the bone marrow microenvironment in vitro we can better control the expansion and differentiation of these cells. In this work, derivatives of poly(ethylene glycol) diacrylate hydrogels were used as a culture substrate for hematopoietic stem and progenitor cell (HSPC) populations. Key HSC cytokines, stem cell factor (SCF) and interferon-γ (IFNγ), as well as the cell adhesion ligands RGDS and connecting segment 1 were covalently immobilized onto the surface of the hydrogels. With the use of SCF and IFNγ, we observed significant expansion of HSPCs, ∼97 and ∼104 fold respectively, while maintaining c-kit(+) lin(-) and c-kit(+) Sca1(+) lin(-) (KSL) populations and the ability to form multilineage colonies after 14 days. HSPCs were also encapsulated within degradable poly(ethylene glycol) hydrogels for three-dimensional culture. After expansion in hydrogels, ∼60% of cells were c-kit(+), demonstrating no loss in the proportion of these cells over the 14 day culture period, and ∼50% of colonies formed were multilineage, indicating that the cells retained their differentiation potential. The ability to tailor and use this system to support HSC growth could have implications on the future use of HSCs and other blood cell types in a clinical setting.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polietilenglicoles / Células Madre Hematopoyéticas / Técnicas de Cultivo de Célula / Hidrogeles Idioma: En Revista: Biotechnol Bioeng Año: 2016 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polietilenglicoles / Células Madre Hematopoyéticas / Técnicas de Cultivo de Célula / Hidrogeles Idioma: En Revista: Biotechnol Bioeng Año: 2016 Tipo del documento: Article