Details

Autor(en) / Beteiligte

• Isern, Joan
• Martín-Antonio, Beatriz
• Ghazanfari, Roshanak
• Martín, Ana M.
• López, Juan A.
• del Toro, Raquel
• Sánchez-Aguilera, Abel
• Arranz, Lorena
• Martín-Pérez, Daniel
• Suárez-Lledó, María
• Marín, Pedro
• Van Pel, Melissa
• Fibbe, Willem E.
• Vázquez, Jesús
• Scheding, Stefan
• Urbano-Ispizúa, Álvaro
• Méndez-Ferrer, Simón

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2013-05, Vol.3 (5), p.1714-1724

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Human MSCs can be simply isolated, preserved, and expanded as nonadherent mesenspheres•Human bone marrow mesenspheres derive from CD45−CD31−CD71−CD146+CD105+ nestin+ cells•Human mesenspheres expand hematopoietic stem cells (HSCs) through secreted factors•Mesensphere attachment to plastic changes their phenotype and decreases HSC support In this study, Méndez-Ferrer and colleagues report a method of isolating and culturing human mesenchymal stem cells (MSCs) as nonadherent clonal spheres. Human mesenspheres could simply be grown from bone marrow CD45neg-enriched cells. In culture conditions where they displayed a primitive phenotype and decreased adherence to plastic, they promoted expansion of blood stem cells through secreted factors. This method may preserve the self-renewal of human MSCs and their ability to support functional blood stem cells in culture.