Abstract
Abstract Normal human bone marrow stroma cells include stem cells for both hematopoietic and osteochondrogenic lineages and express both bone morphogenetic protein (BMP) type I and II receptors. As a member of the TGF-beta superfamily, BMP-6 binds to both BMP receptors and is involved in the developmental processes of renal and hepatic systems as well as of human fetal intestine. BMP-6 induces osteoblastic differentiation of pluripotent mesenchymal stem cells and is an autocrine stimulator of chondrocyte differentiation. The present study was carried out to investigate the effect of BMP-6 on human cobblestone-area-forming cells (CAFC), which represent the functional primitive repopulating hematopoietic stem cell in long-term marrow culture. The effect of BMP-6 on marrow stroma production of interleukin-6, interleukin-11 and their common transducing receptor gp130, which is expressed in primitive hematopoietic stem cells and is indispensable for the proliferation and tri-lineage differentiation of these hematopoietic stem cells, was examined. The effect of BMP-6 on marrow stroma release of soluble adhesion molecule VCAM-1 mediating the primitive hematopoietic stem cell adhesion to marrow stroma was examined. The number of CAFC was significantly reduced after BMP-6 treatment from 88 ± 10 in control cultures in a dose-dependent manner to only 48 ± 3 per 105 cells in 50 ng/ml BMP-6– treated marrow stroma cultures, p + cells in normal individuals. Also, we previously observed a significantly lower expression of VLA4 (CD49d) on G-CSF-mobilized CD34 + cells in the peripheral blood than on bone marrow CD34 + before mobilization in the same individuals. BMPs are currently being used in clinical trials for bone repair and fracture healing; the present results suggest a possible novel therapeutic role for BMP-6 in mobilizing CD34 − cells for transplantation. However, the potential therapeutic use of BMP-6 as a mobilizing agent should only be applied in patients with myeloid leukemia and not other tumors due to the expression of BMP-6 in solid tumors and lack of BMP expression in myeloid leukemia cells.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
