1. Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion
- Author
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Joan Isern, Beatriz Martín-Antonio, Roshanak Ghazanfari, Ana M. Martín, Juan A. López, Raquel del Toro, Abel Sánchez-Aguilera, Lorena Arranz, Daniel Martín-Pérez, María Suárez-Lledó, Pedro Marín, Melissa Van Pel, Willem E. Fibbe, Jesús Vázquez, Stefan Scheding, Álvaro Urbano-Ispizúa, and Simón Méndez-Ferrer
- Subjects
Biology (General) ,QH301-705.5 - Abstract
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.
- Published
- 2013
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