Hematopoietic and nonhematopoietic potentials of Hoechst(low)/side population cells isolated from adult rat kidney

Abstract

Background: Although the regenerative stem cell is expected to exist in many adult tissues, the cell contributing to the regeneration of the kidney remains unknown in its type and origin.

Methods: In this study, we isolated cells that show low stain with a DNA-binding dye Hoechst 33342 (Hoechst(low) cells) from adult rat kidney, and investigated their differentiation potentials.

Results: Hoechst(low) cells, generally termed side population cells, existed at a frequency of 0.03% to 0.1% in the cell suspension of the digested kidney. Analysis of the kidney-derived Hoechst(low) cells after bone marrow transplantation indicated that some of the cells were derived from bone marrow. When enhanced green fluorescent protein (EGFP)-labeled kidney-derived Hoechst(low) cells were intravenously transplanted into wild-type adult rats, EGFP(+) cells were not detected in the kidney, but EGFP(+) skeletal muscle, EGFP(+) hepatocytes and EGFP(+) bone marrow cells were observed. Even after the induction of the experimental glomerulonephritis and gentamicin-induced nephropathy that promote the differentiation of bone marrow-derived cells into repopulating mesangial cells and tubular component cells, respectively, EGFP(+) mesangial or tubular cells were not observed. Neither with an in vitro system, which we established to produce mesangial-like cells from crude bone marrow culture, did Hoechst(low) cells yield mesangial-like cells.

Conclusion: These findings implicate that Hoechst(low) cells in the kidney may have potentials for hematopoietic and nonhematopoietic lineages, but are not stem cells for renal cells, especially mesangial and tubular cells.