title: BMP-7 improved proliferation and hematopoietic reconstitution potential of ex vivo expanded cord blood-derived CD34(+) cells.
abstract: Due to limited availability, ex vivo expansion is essential for clinical applications of hematopoietic stem cells (HSCs). Bone morphogenetic proteins (BMPs) play an important role in regulating hematopoiesis development. In this study, the effects of BMP-2 and BMP-7 at different doses on expansion, clonogenicity and differentiation of cord blood (CB)-derived CD34(+) cells were investigated in serum-free medium supplemented with stem cell factor, thrombopoietin and flt3-ligand (STF). Irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice were used as an animal model to assess the in vivo hematopoietic reconstitution potential of CB-derived CD34(+) cells treated by BMPs. It was demonstrated that the addition of BMP-7 at 5 ng/mL improved the proliferations of total cells, CD34(+) cells and CD34(+)CD38(-) cells without affecting the colony-forming ability of CD34(+) cells and component of lineage cells, while BMP-2 showed no effect on expanding these cells during the 10-day culture. Moreover, CB-derived CD34(+) cells cultured with STF and 5 ng/mL BMP-7 for 10 days were transplanted into irradiated NOD/SCID mice, and showed better engraftment and multi-lineage reconstitution ability compared with the cells cultured with STF alone. Together, 5 ng/mL BMP-7 was beneficial to ex vivo expansion of CB-derived CD34(+) cells for clinical purposes. The results may help improve the existing culture systems and achieve wider application of HSCs.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Postbox 309#, 130 Meilong Road, Shanghai, 200237, People's Republic of China.
authors.forename: Yue-Han
authors.initials: YH
authors.lastname: Su
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Cai
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Ye
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Tan
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D018952:Antigens, CD34; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7