Brouard N, Chapel A, Thierry D, Charbord P, Péault B
Institut de Protection et de Sûreté Nucléaire, Département de Protection de la Santé de l'Homme et de Dosimétrie, Fontenay-aux-Roses, France.
J Hematother Stem Cell Res. 2000 Apr;9(2):175-81. doi: 10.1089/152581600319388.
Transplantation of BM stromal cells engineered to secrete therapeutic factors could represent a treatment for a large array of hematologic disorders. The aim of this study was to evaluate the susceptibility of human BM stromal cell precursors to retroviral gene transfer, then the ability of those to be transplanted in vivo. We have transduced a recombinant retrovirus encoding the mouse CD2 antigen into STRO-1+ cells selected from adult and fetal BM. Gene-modified stromal cells were injected intravenously into NOD-SCID mice engrafted previously with pieces of human fetal hematopoietic bone. Using nested PCR, transgenic human cells were detected both in the marrow of human bone grafts and in the BM, liver, and spleen of host mice 7 weeks after grafting. These data indicate that BM stromal progenitor cells are targets for retrovirus-mediated gene transfer and can home to hematopoietic tissues on engraftment through the bloodstream of nonconditioned hosts.
经基因工程改造以分泌治疗因子的骨髓基质细胞移植，可能成为治疗多种血液系统疾病的一种方法。本研究的目的是评估人类骨髓基质细胞前体细胞对逆转录病毒基因转移的易感性，以及这些细胞在体内的移植能力。我们将编码小鼠CD2抗原的重组逆转录病毒转导到从成人和胎儿骨髓中筛选出的STRO-1+细胞中。将基因修饰的基质细胞静脉注射到预先植入人胎儿造血骨块的NOD-SCID小鼠体内。通过巢式PCR检测发现，移植7周后，在人骨移植物的骨髓以及宿主小鼠的骨髓、肝脏和脾脏中均检测到转基因人类细胞。这些数据表明，骨髓基质祖细胞是逆转录病毒介导的基因转移的靶细胞，并且在植入后可通过未预处理宿主的血流归巢至造血组织。
