Grassinger Jochen, Simon Michaela, Mueller Gunnar, Drewel Diana, Andreesen Reinhard, Hennemann Burkhard
Department of Hematology and Oncology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93042 Regensburg, Germany.
Cytokine. 2007 Dec;40(3):165-71. doi: 10.1016/j.cyto.2007.09.004. Epub 2007 Oct 29.
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.
骨形态发生蛋白(BMPs)调控造血的发育程序。我们证明了在培养的CD34+细胞上骨形态发生蛋白受体Ia和II的表达增加,并研究了BMP-2、-4和-7对用干细胞因子、flt3配体和白细胞介素-3(SF3)培养的产后造血祖细胞(HPC)的影响。在含有SF3的无血清培养基中添加5、25和50 ng/ml的BMP-2,7天后CD34+细胞增加了1.4至1.2倍,但未观察到对集落形成细胞(CFC)或长期培养起始细胞(LTC-IC)有影响。25 ng/ml的BMP-4在1周内诱导集落形成细胞(CFC)扩增2.9倍,随后在第14天降至预培养值。从第0天到第14天,长期培养起始细胞(LTC-IC)的数量减少了40倍。5至50 ng/ml的BMP-7对CD34+细胞和CFC的扩增没有影响,但与单独使用SF3相比,5 ng/ml的BMP-7显著提高了LTC-IC的存活率。总之,BMP-2、-4和-7对用无血清培养基和SF3培养的CD34+细胞和CFC的增殖没有影响。然而,BMP-7而非BMP-2和BMP-4可防止在无血清培养基加SF3中培养的原始造血祖细胞的丢失。