Pereira R F, Halford K W, O'Hara M D, Leeper D B, Sokolov B P, Pollard M D, Bagasra O, Prockop D J
Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Proc Natl Acad Sci U S A. 1995 May 23;92(11):4857-61. doi: 10.1073/pnas.92.11.4857.
Cells from transgenic mice expressing a human mini-gene for collagen I were used as markers to follow the fate of mesenchymal precursor cells from marrow that were partially enriched by adherence to plastic, expanded in culture, and then injected into irradiated mice. Sensitive PCR assays for the marker collagen I gene indicated that few of the donor cells were present in the recipient mice after 1 week, but 1-5 months later, the donor cells accounted for 1.5-12% of the cells in bone, cartilage, and lung in addition to marrow and spleen. A PCR in situ assay on lung indicated that the donor cells diffusely populated the parenchyma, and reverse transcription-PCR assays indicated that the marker collagen I gene was expressed in a tissue-specific manner. The results, therefore, demonstrated that mesenchymal precursor cells from marrow that are expanded in culture can serve as long-lasting precursors for mesenchymal cells in bone, cartilage, and lung. They suggest that cells may be particularly attractive targets for gene therapy ex vivo.
表达人I型胶原蛋白微型基因的转基因小鼠的细胞被用作标记物，以追踪来自骨髓的间充质前体细胞的命运，这些细胞通过贴壁于塑料培养皿而部分富集，在培养中扩增，然后注射到受辐照的小鼠体内。针对标记物I型胶原蛋白基因的灵敏PCR检测表明，1周后受体小鼠体内几乎没有供体细胞，但1至5个月后，除了骨髓和脾脏外，供体细胞在骨、软骨和肺中的细胞中占1.5%至12%。对肺进行的PCR原位检测表明供体细胞弥漫性地分布于实质组织中，逆转录PCR检测表明标记物I型胶原蛋白基因以组织特异性方式表达。因此，结果表明在培养中扩增的来自骨髓的间充质前体细胞可作为骨、软骨和肺中间充质细胞的长期前体。它们表明这些细胞可能是离体基因治疗特别有吸引力的靶点。
