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

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.

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.

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.

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.