MARROW STROMAL CELLS AS A SOURCE OF PROGENITOR CELLS FOR NONHEMATOPOIETIC TISSUES IN TRANSGENIC MICE WITH A PHENOTYPE OF OSTEOGENESIS IMPERFECTA

Marrow stromal cells from wild-type mice were infused into transgenic mice that had a phenotype of fragile bones resembling osteogenesis imp erfecta because they expressed a human minigene for type I collagen, I n mice that were irradiated with potentially lethal levels (700 cGy) o r sublethal levels (350 cGy), DNA from the donor marrow stromal cells was detected consistently in marrow bone, cartilage, and lung either 1 or 2.5 mo after the infusions, The DNA also was detected but less fre quently in the spleen, brain, and skin, There was a small but statisti cally significant increase in both collagen content and mineral conten t of bone 1 mo after the infusion, Similar results were obtained with infusion of relatively large amounts of wild-type whole marrow cells i nto the transgenic mice, In experiments in which male marrow stromal c ells were infused into a female osteogenesis imperfecta-transgenic mou se, fluorescense in situ hybridization assays for the Y chromosome ind icated that, after 2.5 mo, donor male cells accounted for 4-19% of the fibroblasts or fibroblast-like cells obtained in primary cultures of the lung, calvaria, cartilage, long bone, tail, and skin, In a paralle l experiment in which whole marrow cells from a male mouse were infuse d into a female immunodeficient rag-2 mouse, donor male cells accounte d for 4-6% of the fibroblasts or fibroblast-like cells in primary cult ures, The results support previous suggestions that marrow stromal cel ls or related cells in marrow serve as a source for continual renewal of cells in a number of nonhematopoietic tissues.