Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion.

Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isol...

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Detalhes bibliográficos
Autores: Isern, Joan, Martín-Antonio, Beatriz, Ghazanfari, Roshanak, Martín, Aan M., López, Juan A., Toro, Raquel del, Sánchez-Aguilera, Abel, Arranz, Lorena, Martín-Pérez, Daniel, Suárez-Lledó Grande, María, Marín, Pedro, Van Pel, Melissa, Fibbe, Willem E., Vázquez, Jesús, Scheding, Stefan, Urbano Ispizua, Álvaro, Méndez-Ferrer, Simón
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/51084
Acesso em linha:https://hdl.handle.net/2445/51084
Access Level:acceso abierto
Palavra-chave:Diferenciació cel·lular
Hematopoesi
Medul·la òssia
Cell diferentiation
Hematopoiesis
Bone marrow
Descrição
Resumo:Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45- CD31- CD71- CD146+ CD105+ nestin+ cells but could also be simply grown from fetal and adult BM CD45--enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.

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