Bone morphogenetic protein (BMP)-7 but not BMP-2 and BMP-4 improves maintenance of primitive peripheral blood-derived hematopoietic progenitor cells (HPC) cultured in serum-free medium supplemented with early acting cytokines

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2007-12, Vol.40 (3), p.165-171
• Main Authors: Grassinger, Jochen, Simon, Michaela, Mueller, Gunnar, Drewel, Diana, Andreesen, Reinhard, Hennemann, Burkhard
• Format: Article
• Language: English
• Subjects: Antigens, CD34 - biosynthesis; Bone morphogenetic protein; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Protein Receptors, Type I - biosynthesis; Bone Morphogenetic Protein Receptors, Type II - biosynthesis; Bone Morphogenetic Proteins - pharmacology; Cell differentiation; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hematopoiesis; Hematopoiesis - drug effects; Hematopoiesis - physiology; Hematopoietic progenitor cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Infant, Newborn; Interleukin-3 - pharmacology; Membrane Proteins - pharmacology; Stem Cell Factor - pharmacology; Time Factors; Transforming Growth Factor beta - pharmacology
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2007.09.004

BMPs regulate the developmental program of hematopoiesis. We demonstrate an increased expression of the BMP receptors Ia and II on cultured CD34 + cells and examine the impact of BMP-2, -4 and -7 on postnatal HPC cultured with stem cell factor, flt3-ligand and interleukin-3 (SF3). The addition of BMP-2 at 5, 25 and 50 ng/m to serum-free medium with SF3 yielded a 1.4- to 1.2-fold increase of CD34 + cells after seven days, but no effect on CFC or LTC-IC was observed. BMP-4 at 25 ng/ml induced a 2.9-fold expansion of colony-forming cells (CFC) within 1 week followed by a decrease to pre-culture values on day 14. The number of long-term culture initiating cells (LTC-IC) decreased by the factor 40 from day 0 to day 14. BMP-7 at 5–50 ng/ml had not effect on the expansion of CD34 + cells and CFC, but improved at 5 ng/ml the survival of LTC-IC significantly as compared to SF3 alone. In summary, BMP-2, -4 and -7 have no effect on the proliferation of CD34 + cells and CFC cultured with serum-free medium and SF3. However, BMP-7 but not BMP-2 and BMP-4 prevents the loss of primitive hematopoietic progenitor cells cultured in SFM plus SF3.