摘要
第一代细胞疗法是成熟血细胞的全血输注,以后逐渐发展为成分输血。第二代细胞疗法是包括骨髓、动员外周血及脐带血的造血干细胞移植。近年来,体外扩增造血祖细胞的技术方法已逐渐成熟,在液体培养体系中加入FL(Flt-3 ligand),SCF,IL-1,IL-3,GM-CSF,G-CSF,Epo等细胞因子,可使细胞总数及各系祖细胞得以大量扩增,部分技术方法还可明显地扩增原始的早期祖细胞,(LTC-IC,CD34^+CD38^-细胞,CFU-GEMM等),如FL,Epo等细胞因子的组合,CD34^+CD38^-细胞亚群的扩增,负调控因子(如TGF-β,LIF及MIP-1α,IL-8,PF4等趋化因子)的应用,基质细胞的支持和继续灌注培养等。此外,利用上述细胞因子和FL,SCF,G-CSF,Epo,Tpo IL-4,FNF-α,IL-7,IL—15等的不同组合,还可定向地诱导CD34^+细胞向粒系、红系、巨核系/血小板、NK细胞、树突状细胞(dendritic cells,DC)及淋巴细胞等方向分化与扩增。这些技术方法与方案已开始进入临床试用,在造血调控研究,造血干细胞移殖,大剂量化疗后的造血细胞支持治疗,肿瘤生物免疫治疗,基因治疗等领域将具有广阔的应用前景。
Cellular therapeutics began with mature blood cells, first with whole blood and then later evolving to the use of fractionated blood components. The second phase of cellular therapeutics was stem cell transplantation from bone marrow, mobilized peripheral blood, and umbilical cord blood. Over the last few years, techniques have become available, which allow the extensive proliferation of hematopoietic progenitor cells in ex vivo culture systems. The most commonly used method involves a liquid suspension culture system supplemented with a range of cytokines such as FL (Flt-3 ligand), SCF, IL-1, IL-3, GM-CSF, G-CSF and Epo. Large increases in total cell numbers and committed progenitor cells can be readily obtained and, with some techniques, including the combination of FL and Tpo, the expansion of CD34+ CD38~ subset, the addition of some hematopoietic in-hibitors(such as TGF-β, LIF and MlP-1α, IL-8, PF4 of chemokines), stromal-based expansion culture and continuous perfusion cultures, significant expansion of primitive hematopoietic cells (LTC-IC, CD34 + CD38~ cells, CFU-GEMM) has been demonstrated. It is possible to induce CD34+ cells to proliferateand differentiate committedly into granulocytes, erythrocytes, megakaryocytes/platelets, NK cells, dendritic cells and lymphocytes with different combinations of cytokines (FL, SCF, G-CSF, Epo, Tpo, IL-4, TNF-α, IL-7, IL-15, etc). These techniques have now developed to the point at which clinical trials are now underway in a variety of settings for the applications of hematopoietic regulation research, hematopoietic stem cell transplantation, hematopoietic support after high-dose chemotherapy, bio-immunotherapy of cancers, and gene therapy.
出处
《中国实验血液学杂志》
CAS
CSCD
1998年第1期1-5,共5页
Journal of Experimental Hematology
关键词
细胞疗法
造血祖细胞
体外扩增
诱导分化
造血生长因子
cellular therapeutics
hematopoietic progenitor cell
ex vivo expansion
induced differentiation
hematopoietic growth factor
