BMP4: A Stem Cell Therapy Growth Factor (Cytokine)

Overall Introduction of BMP4 Growth Factor

BMP4 belong to the transformation growth factor beta (TGFβ) superfamily. is involved in regulation of cell proliferation, differentiation, and apoptosis of stem cells, including Embryonic Stem (ES) cells, hematopoieti Stem (ES) cells, Mesenchymal Stem (ES) cells and Neural Stem (ES) cells. So BMP4 play an essential role in stem cell therapy.

BMP4 Effects on Embryonic Stem (ES) cells Differentiation

BMP4 induces the differentiation of human embryonic stem cells to trophoblast. DNA microarray, RT-PCR, and immunoassay analyses demonstrate that the differentiated cells express a range of trophoblast markers and secrete placental hormones. When plated at low density, the BMP4-treated cells form syncytia that express chorionic gonadotrophin (CG). These results underscore fundamental differences between human and mouse embryonic stem cells, which differentiate poorly, if at all, to trophoblast. Human embryonic stem cells thus provide a tool for studying the differentiation and function of early human trophoblast and could provide a new understanding of some of the earliest differentiation events of human postimplantation development.
The major effect of BMP4 on the self-renewal of embryonic stem cells is accomplished by means of the inhibition of both extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways, and inhibitors of ERK and p38 MAPKs mimic the effect of BMP4 on embryonic stem cells. Importantly, inhibition of the p38 MAPK pathway by SB203580 overcomes the block in deriving embryonic stem cells from blastocysts lacking a functional Alk3, the BMP type IA receptor. These results uncover a paradigm for BMP signaling in the biology of pluripotent stem cells.

BMP4 Effects on Hematopoietic Stem (ES) cells

BMP4 hypomorph is used to investigate the role of BMP4 in regulating hematopoietic stem cell (HSC) function and maintaining steady-state hematopoiesis in the adult. Reporter gene expression shows that Bmp4 is expressed in cells associated with the hematopoietic microenvironment including osteoblasts, endothelial cells, and megakaryocytes. Although resting hematopoiesis is normal in a BMP4-deficient background, the number of c-Kit+, Sca-1+, Lineage− cells is significantly reduced. Serial transplantation studies reveal that BMP4-deficient recipients have a microenvironmental defect that reduces the repopulating activity of wild-type hematopoietic stem cells. This defect is even more pronounced in a parabiosis model that demonstrates a profound reduction in wild-type hematopoietic cells within the bone marrow of BMP4-deficient recipients. Furthermore, wild-type hematopoietic stem cells that successfully engraft into the BMP4-deficient bone marrow show a marked decrease in functional stem cell activity when tested in a competitive repopulation assay. Taken together, these findings indicate BMP4 is a critical component of the hematopoietic microenvironment that regulates both hematopoietic stem cell number and function.

BMP4 Effects on Mesenchymal Stem (ES) cells

BMP4 belongs to the group of bone morphogenetic proteins (BMPs), i.e. growth factors of the TGF-ß superfamily that are involved in fate decisions of mesenchymal stem cells. While BMP4 is known to act as an inductor of adipocyte lineage commitment there is ample evidence that simple linear pathways are not suited to describe that process. Instead, BMP4 apparently acts within a network of factors finally determining the initial fate decision as well as terminal differentiation of adipocytes.

BMP4 Effects on Neural Stem (ES) cells

BMP4 induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor.

BMP4: A Stem Cell Therapy Growth Factor (Cytokine)-Reference

• Zhang J, Li L. BMP signaling and stem cell regulation[J]. Developmental biology, 2005, 284(1): 1-11.
• Xu R H, et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast[J]. Nature biotechnology, 2002, 20(12): 1261-1264.
• Qi X, Li T G, et al. BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways[J]. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(16): 6027-6032.
• Goldman D C, et al. BMP4 regulates the hematopoietic stem cell niche[J]. Blood, 2009, 114(20): 4393-4401.
• Markowski D N, et al. BMP4 increases expression of HMGA2 in mesenchymal stem cells[J]. Cytokine, 2011, 56(3): 811-816.
• Moon B S, et al. Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway[J]. Experimental & molecular medicine, 2009, 41(2): 116-125.