Limited contribution of circulating cells to the development and maintenance of nonhematopoietic bovine tissues

Bone marrow-derived stem cells appear surprisingly multipotent in experimental settings, but the physiological significance of such plasticity is unclear. We have used sex-mismatched cattle twins with stably chimeric hematopoietic systems to investigate the general extent of integration of circulating cells to the nonhematopoietic cell lineages in an unmanipulated large mammal. The donor-derived (Y+) nonhematopoietic cells in female recipient tissues were visualized by Y-chromosome specific in situ hybridization combined with pan-leukocyte labeling. Y+ leukocytes were frequent in all tissues, but in 11 of 12 animals, average contribution to nonhematopoietic lineages was in any tissue below 1% (in brain <0.001%). Significantly higher integration rate was detected in regenerating granulation tissue. Also, one animal showed a high frequency of nonhematopoietic Y+ cells in several tissues, including intestinal epithelium and mammary gland stroma. In conclusion, circulating cells do not appear significant in the development and maintenance of nonhematopoietic bovine tissues, but may be important in regeneration and other special conditions.