The phenotypic fate of bone marrow-derived stem cells in acute kidney injury.

ABSTRACT

BACKGROUND: Despite increasing attention on the role of bone marrow derived stem cells in repair or rejuvenation of tissues and organs, cellular mechanisms of such cell-based therapy remain poorly understood. METHODS: We reconstituted hematopoiesis in recipient C57BL/6J mice by transplanting syngeneic GFP(+) bone marrow (BM) cells. Subsequently, the recipients received subcutaneous injection of granulocyte-colony stimulating factor (G-CSF) and were subjected to acute renal ischemic injury. Flow cytometry and immunostaining were performed at various time points to assess engraftment and phenotype of BM derived stem cells. RESULTS: Administration of G-CSF increased the release of BM derived stem cells into circulation and enhanced the ensuing recruitment of BM derived stem cells into injured kidney. During the second month post injury, migrated BM derived stem cells lost hematopoietic phenotype (CD45) but maintained the expression of other markers (Sca-1, CD133 and CD44), suggesting their potential of transdifferentiation into renal stem cells. Moreover, G-CSF treatment enhanced the phenotypic conversion. CONCLUSION: Our work depicted a time-course dependent transition of phenotypic characteristics of BM derived stem cells, demonstrated the existence of BM derived stem cells in damaged kidney and revealed the effects of G-CSF on cell transdifferentiation.