Davis T A, Black A T, Kidwell W R, Lee K P
Immune Cell Biology Program, Stem Cell Biology Branch, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Cytokine. 1997 Apr;9(4):263-75. doi: 10.1006/cyto.1996.0163.
The authors have recently shown that direct contact with primary porcine microvascular endothelial cell monolayers (PMVECs) in combination with haematopoietic growth factors enhances the expansion of primitive human haematopoietic CD34+ bone marrow progenitor cells. It is now demonstrated that serum-free conditioned medium (PMVEC CM, concentrated 70x for proteins >30 kDa) from untreated PMVECs contains haematopoietic growth factor activity that enhances the in vitro proliferation, haematopoietic cell production, and colony cell formation of primitive human haematopoietic progenitor cells. In combination with exogeneously added human growth factors such as interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and EPO, PMVEC CM enhances the proliferation and colony growth of human haematopoietic CD34+ cells. In contrast, PMVEC CM has no significant synergistic activity on either stem cell factor (SCF) or flt3-ligand-induced CD34+ cell proliferation, cell production or colony formation. Blocking mAbs against the c-kit receptor have no effect on PMVEC CM-induced CD34+ cell proliferation at titres that completely suppress SCF-induced proliferation. Moreover, it is shown that this haematopoietic growth factor supports the proliferation and colony formation of murine, non-human primate, and porcine marrow progenitor cells without any apparent species-specific restrictions in its activity. These finding suggest that PMVEC CM contains a novel early haematopoietic activity.
作者最近发现,与造血生长因子联合使用时,直接接触原代猪微血管内皮细胞单层(PMVECs)可增强原始人类造血CD34+骨髓祖细胞的扩增。现已证明,未经处理的PMVECs的无血清条件培养基(PMVEC CM,蛋白质>30 kDa的浓缩70倍)含有造血生长因子活性,可增强原始人类造血祖细胞的体外增殖、造血细胞生成和集落细胞形成。与外源性添加的人类生长因子如白细胞介素3(IL-3)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和促红细胞生成素(EPO)联合使用时,PMVEC CM可增强人类造血CD34+细胞的增殖和集落生长。相比之下,PMVEC CM对干细胞因子(SCF)或flt3配体诱导的CD34+细胞增殖、细胞生成或集落形成没有显著的协同活性。针对c-kit受体的阻断单克隆抗体在完全抑制SCF诱导的增殖的效价下,对PMVEC CM诱导的CD34+细胞增殖没有影响。此外,研究表明,这种造血生长因子支持小鼠、非人灵长类动物和猪骨髓祖细胞的增殖和集落形成,其活性没有任何明显的物种特异性限制。这些发现表明,PMVEC CM含有一种新的早期造血活性。