造血因子基因修饰的基质细胞诱导造血细胞向巨核系细胞定向扩增的研究  

Stromal cells modified by thrombopoietin and/or interleukin-11 gene to regulate the megakaryocytopoiesis

作　　者：杨光[1] 周雅德[1] 裴雪涛[2] 李梁[2] 

机构地区：[1]重庆医科大学儿童医院,400014 [2]北京军事医学科学院放射研究所野战输血研究所国家生物医学分析中心

出　　处：《中华儿科杂志》2000年第12期729-732,共4页Chinese Journal of Pediatrics

基　　金：国家重点基础研究发展规划项目!(973) (G19990 5 390 3);国家杰出青年科学基金!(3982 5 111)资助

摘　　要：目的　为诱导造血细胞在体外向巨核系细胞定向扩增 ,观察了促血小板生成素 (TPO)、白细胞介素 11(IL 11)基因修饰的成纤维样基质细胞 (HFCL)对纯化的脐血CD+34 造血细胞向巨核系细胞定向增殖分化的影响。方法　以未经造血因子修饰的HFCL支持的造血细胞体外扩增作为对照 ,采用流式细胞仪检测脐血CD+34 造血细胞在TPO基因修饰的HFCL(TPO/HFCL)、IL 11基因修饰的HFCL(IL 11/HFCL)以及TPO和IL 11基因共修饰的HFCL(TPO +IL 11/HFCL)的支持下 ,经过 7d的体外扩增后 ,扩增细胞中的CD+34 CD+4 1巨核系祖细胞和表型为CD+4 1CD+61较成熟的巨核系细胞的比例。结果　脐血CD+34 造血细胞经过 7d体外扩增后 ,CD+34 CD+4 1巨核系祖细胞在TPO/HFCL、IL 11/HFCL和TPO +IL11/HFCL支持的扩增细胞中的比例分别为 (13.7± 2 .0 ) %、(9.9± 1.1) %、(14.5± 2 .0 ) % ,高于HFCL的 (6 .5± 1.8) % (P <0 .0 1) ;并表现为TPO/HFCL支持的扩增细胞中巨核系祖细胞的比例高于IL 11/HFCL(P <0 .0 5 )。而表型为CD+4 1CD+61的巨核系细胞在扩增细胞中的比例分别为 (11.9±0 .7) %、(2 4.1± 3 .1) %、(17.6± 1.9) % ,其中IL 11/HFCL和TPO +IL 11/HFCL支持的扩增体系高于HFCL的 (10 .6± 1.5 ) % (P <0 .0 1) ;且IL 11/HFCL对CD+4Objective Delayed platelet recovery after hematopoietic stem cells transplantation is the major problem related to the transplantation success. Thus, it is necessary to promote ex vivo expansion of the megakaryocyte cell line, especially CD + 34 CD + 41 committed megakaryocyte progenitors which have the close relationship with the platelet recovery after the transplantation. In this study, the auther evaluated the effects of stromal cells modified by thrombopoietin (TPO)gene and/or interleukin-11 gene on ex vivo expansion of megakaryocytic cells. Methods The purified CD + 34 hematopoietic cells from cord blood were expanded with the genes modified HFCL in the combination of exogenous interleukin-3, stem cell factor and Fit ligand for seven days. Results The proportions of CD + 34 CD + 41 committed megakaryocyte progenitors were 13.9%, 9.9%, and 14.5%, which were corresponded to 16-fold , 12-fold and 21-fold increases, respectively, and were higher than those of the nontransduced HFCL(6.5% and 7-fold increase). Compared with 10.6% and a 16-fold increase of the nontransduced HFCL, the proportions of more matured CD + 41 CD + 61 megakaryocytes were 11.9%, 24.1%, and 17.6%, which were corresponded to a 21-fold, 42-fold and 28-fold increases, respectively. Conclusion The stromal cells modified by TPO and/or IL-11 gene showed the ability to enhance the growth of CD + 34 CD + 41 megakaryocyte-committed progenitor cells, especially the cells modified by TPO gene, and revealed a less effect on the more maturation processes, especially those modified by IL-11 gene. The stromal cells cotransduced by TPO and IL-11 genes showed a synergistic effect on the expansion of megakaryocytic cells.

关 键 词：造血细胞 TPO IL-11 基质细胞 基因修饰 

分 类 号：R457[医药卫生—治疗学]