Abstract 15346: Human Peripheral blood-derived Sphere as a Niche for Adult Stem-Progenitor Cell Self-Renewal
Background: Human peripheral blood is a promising source of autologous stem-progenitor cells such as endothelial progenitor cells or hematopoietic stem cells However, the rarity of stem cell population and lack of effective method to expand or differentiate it remained a major hurdle for its application. Recently, Spheroid cultures of various stem-progenitor cells have been successfully used to expand or differentiate stem cells in embryonic, cardiac, neurogenic and cancer stem cells.
Methods and Results: Here, we described a novel method of stem-progenitor cells expansion using spheroid culture of human peripheral blood mononuclear cells (hPBMCs) without synthetic growth factors or artificial niche. The spheres, termed as `Blood-Born Hematospheres (BBHS). We found that self-renewal of CD34(+), AC133(+) or KDR(+) stem-progenitor cells were localized inside BBHS. Flow cytometry analysis revealed that stem-progenitor cells exponentially increased between day 3 and day 7 during BBHS maturation and these stem-progenitor cells were functional in vitro and in vivo. BBHS consists of heterogenous blood cells and CD14(+)/CD31(+) cells were found to be the cellular component of BBHS and its exclusion disrupted the sphere formation. Furthermore, BBHS provided natural multi-component of niche for human stem-progenitor cells self-renewal through PECAM-1/PECAM-1 homophilic interaction, subsequent VEGF secretion and extracellular matrix deposition such as Fibronectin, laminin and collagen I,III, and IV.
Conclusion: Our novel strategy of ex vivo expansion of human stem-progenitor cells using self-organized hematopoietic sphere provides an innovative autologous stem cell source and a new model to investigate adult stem cell niche
- © 2010 by American Heart Association, Inc.