LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors
LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors
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DOI：
10.1089/hum.1997.8.12-1417
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发表时间：
1997-08-10
影响因子：
4.2
通讯作者：
Gerson, SL
中科院分区：
文献类型：
--
作者：
Allay, JA;Dennis, JE;Gerson, SL
将含有LacZ和neo基因的逆转录病毒vM5LacZ导入具有成骨和基质分化能力的人骨髓间充质祖细胞(HMPC)，经G418扩增和筛选后，约70%的hMPC共表达LacZ，经G418筛选后，植入SCID小鼠皮下的多孔磷酸钙陶瓷方块中，成骨细胞和成骨细胞中均有LacZ的表达。转导了人白细胞介素3(hIL-3)基因的人巨噬细胞集落刺激因子(HMPC)贴附于陶瓷块上，植入SCID小鼠体内，形成骨并分泌可检测到水平的hIL-3进入体循环至少12周，这些数据表明，基因转导的、培养扩增的骨髓来源的hMPC在体内成骨分化过程中保留了前体表型，并保持了类似的转基因表达水平，因为MPC已被证明分化为骨、软骨和肌腱，这些细胞可能是基因治疗的有用靶点。
Human marrow-derived mesenchymal progenitor cells (hMPCs), which have the capacity for osteogenic and marrow stromal differentiation, were transduced with the myeloproliferative sarcoma virus (MPSV)-based retrovirus, vM5LacZ, that contains the LacZ and neo genes, Stable transduction and gene expression occurred in 18% of cells, After culture expansion and selection in G418, approximately 70% of neo(r) hMPCs co-expressed LacZ, G418-selected hMPC retain their osteogenic potential and form bone in vivo when seeded into porous calcium phosphate ceramic cubes implanted subcutaneously into SCID mice, LacZ expression was evident within osteoblasts and osteocytes in bone developing within the ceramics 6 and 9 weeks after implantation, Likewise, hMPCs transduced with human interleukin-3 (hIL-3) cDNA, adhered to ceramic cubes and implanted into SCID mice, formed bone and secreted detectable levels of hIL-3 into the systemic circulation for at least 12 weeks, These data indicate that genetically transduced, culture-expanded bone marrow-derived hMPCs retain a precursor phenotype and maintain similar levels of transgene expression during osteogenic lineage commitment and differentiation in vivo, Because MPCs have been shown to differentiate into bone, cartilage, and tendon, these cells may be a useful target for gene therapy.