Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift
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.
|Enheter & grupper|
Ämnesklassifikation (UKÄ) – OBLIGATORISK
|Status||Published - 2013|
|Peer review utförd||Ja|
Ingen tillgänglig data
Roshanak Ghazanfari, 2017, Lund: Lund University, Faculty of Medicine. 78 s.
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)