Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice.

TLDR

Mesenchymal precursor cells from marrow were enriched by plastic adherence, expanded in culture, and injected into irradiated mice, with human collagen I mini‑gene markers used to track their fate. After injection, donor cells were undetectable after one week but comprised 1.5–12 % of bone, cartilage, lung, marrow, and spleen cells 1–5 months later, with diffuse lung parenchymal distribution and tissue‑specific collagen I expression, demonstrating that cultured marrow mesenchymal precursors become long‑lasting bone, cartilage, and lung cells and may be useful for ex vivo gene therapy.

Abstract

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.