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

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.

Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells

“…Our data are in good agreement with previously published reports demonstrating that after syngeneic or xenogeneic transplantation of MSCs derived from the bone morrow of mouse, rat or nonhuman primates, donor cells engraft into many tissues of conditioned recipients. [53][54][55][56][57] It is still unclear whether transplanted cells continue to retain their multilineage potentials and clonogenic ability or if they were able to commit into residing tissue. At present, Overall, our results provide evidence supporting the suitability of genetically corrected MSCs by ODN in cellbased therapeutic applications.…”

Gene therapy approaches for osteogenesis imperfecta

“…Normal transplanted cells may also possess survival advantage over the endogenous cells because they synthesize normal matrix. 37 The above hypotheses were initially tested in mice. Bone marrow-derived mesenchymal stem cells or stromal cells harvested from transgenic mice expressing a human truncated or minigene for proa1 (I) collagen were infused into irradiated mice.…”

“…Bone marrow-derived mesenchymal stem cells or stromal cells harvested from transgenic mice expressing a human truncated or minigene for proa1 (I) collagen were infused into irradiated mice. 37 PCR assays to follow the fate of the cells expressing the minigene were used to locate the cells in different tissues of the recipient mice. At 1-5 months after cell infusion, 1.5-12% of the cells in various tissues including bones of the recipient mice were reported to be from the donor.…”

“…At 1-5 months after cell infusion, 1.5-12% of the cells in various tissues including bones of the recipient mice were reported to be from the donor. 37 In subsequent studies, bone marrow stromal cells were harvested from wild-type mice and infused into the transgenic mice expressing the human collagen proa1 (I) minigene. At 2 1 2 months after cell infusion, 4-19% of the cells in various tissues including the bones of the recipient mice were reported to be of donor origin.…”

“…Previous studies in mice and humans have demonstrated that bone marrow-derived mesenchymal stem cells will migrate to bone when administered systemically. [37][38][39]46 We previously showed that direct injection of the cells into the mouse bone marrow cavity leads to a wide distribution of the cells in different tissues of the host. 39 Since early treatment for OI will be essential, mesenchymal stem cells transduced with therapeutic genes will need to be delivered early during development.…”