Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6643
Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion
Isern, Joan CNIC | Martín-Antonio, Beatriz | Ghazanfari, Roshanak | Martin, Ana M. CNIC | Lopez, Juan Antonio CNIC | Del Toro, Raquel CNIC | Sanchez-Aguilera, Abel CNIC | Arranz, Lorena CNIC | Martin-Perez, Daniel CNIC | Suárez-Lledó, María | Marín, Pedro | Van Pel, Melissa | Fibbe, Willem E | Vazquez, Jesus CNIC | Scheding, Stefan | Urbano-Ispizúa, Álvaro | Mendez-Ferrer, Simon CNIC
Cell Rep. 2013 May 30;3(5):1714-24
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.
Animals | Antigens, CD | Bone Marrow Cells | Cell Differentiation | Cell Lineage | Cells, Cultured | Coculture Techniques | Fetal Blood | Hematopoietic Stem Cells | Humans | Mesenchymal Stromal Cells | Mice | Mice, Inbred NOD | Nestin
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