Uterine-Derived Stem Cells Reconstitute the Bone Marrow of Irradiated Mice

Abstract

Hematopoietic stem cells (HSCs) can be found in several tissues of mesodermal origin. Uterine tissue contains stem cells and can regenerate during each menstrual cycle with robust new tissue formation. Stem cells may play a role in this regenerative potential. Here, we report that transplantation of cells isolated from murine uterine tissue can rescue lethally irradiated mice and reconstitute the major hematopoietic lineages. Donor cells can be detected in the blood and hematopoietic tissues such as spleen and bone marrow (BM) of recipient mice. Uterine tissue contains a significant percentage of cells that are Sca-1⁺, Thy 1.2⁺, or CD45⁺ cells, and uterine cells (UCs) were able to give rise to hematopoietic colonies in methylcellulose. Using secondary reconstitution, a key test for hematopoietic potential, we found that the UCs exhibited HSC-like reconstitution of BM and formation of splenic nodules. In a sensitive assay for cell fusion, we used a mixture of cells from Cre and loxP mice for reconstitution and demonstrated that hematopoietic reconstitution by UCs is not a function of fusion with donor BM cells. We also showed that the hematopoietic potential of the uterine tissue was not a result of BM stem cells residing in the uterine tissue. In conclusion, our data provide novel evidence that cells isolated from mesodermal tissues such as the uterus can engraft into the hematopoietic system of irradiated recipients and give rise to multiple hematopoietic lineages. Thus, uterine tissue could be considered an important source of stem cells able to support hematopoiesis.