title: Acellular bone marrow extracts significantly enhance engraftment levels of human hematopoietic stem cells in mouse xeno-transplantation models.
abstract: Hematopoietic stem cells (HSC) derived from cord blood (CB), bone marrow (BM), or mobilized peripheral blood (PBSC) can differentiate into multiple lineages such as lymphoid, myeloid, erythroid cells and platelets. The local microenvironment is critical to the differentiation of HSCs and to the preservation of their phenotype in vivo. This microenvironment comprises a physical support supplied by the organ matrix as well as tissue specific cytokines, chemokines and growth factors. We investigated the effects of acellular bovine bone marrow extracts (BME) on HSC in vitro and in vivo. We observed a significant increase in the number of myeloid and erythroid colonies in CB mononuclear cells (MNC) or CB CD34+ cells cultured in methylcellulose media supplemented with BME. Similarly, in xeno-transplantation experiments, pretreatment with BME during ex-vivo culture of HSCs induced a significant increase in HSC engraftment in vivo. Indeed, we observed both an increase in the number of differentiated myeloid, lymphoid and erythroid cells and an acceleration of engraftment. These results were obtained using CB MNCs, BM MNCs or CD34(+) cells, transplanted in immuno-compromised mice (NOD/SCID or NSG). These findings establish the basis for exploring the use of BME in the expansion of CB HSC prior to HSC Transplantation. This study stresses the importance of the mechanical structure and soluble mediators present in the surrounding niche for the proper activity and differentiation of stem cells.
authors: Department of Biology, Doctoral School of Science and Technology (DSST), Lebanese University, Beirut, Lebanon.
authors: Kazem
authors: K
authors: Zibara
authors: Rima
authors: R
authors: Hamdan
authors: Leila
authors: L
authors: Dib
authors: Steen
authors: S
authors: Sindet-Pedersen
authors: Mohamed
authors: M
authors: Kharfan-Dabaja
authors: Ali
authors: A
authors: Bazarbachi
authors: Marwan
authors: M
authors: El-Sabban
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000737:chemistry*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014183:Transplantation, Heterologous
chemical_list: D045424:Complex Mixtures