Iwatani Hirotsugu, Ito Takahito, Imai Enyu, Matsuzaki Yumi, Suzuki Akira, Yamato Masaya, Okabe Masaru, Hori Masatsugu
Department of Internal Medicine and Therapeutics, Osaka University School of Medicine, Suita, Osaka, Japan.
Kidney Int. 2004 May;65(5):1604-14. doi: 10.1111/j.1523-1755.2004.00561.x.
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.
尽管人们期望再生干细胞存在于许多成体组织中，但对肾脏再生有贡献的细胞，其类型和来源仍不清楚。
在本研究中，我们从成年大鼠肾脏中分离出对DNA结合染料Hoechst 33342染色浅的细胞（Hoechst(low)细胞），并研究了它们的分化潜能。
Hoechst(low)细胞，通常称为侧群细胞，在消化后的肾脏细胞悬液中的存在频率为0.03%至0.1%。对骨髓移植后的肾脏来源的Hoechst(low)细胞进行分析表明，其中一些细胞来源于骨髓。当将增强型绿色荧光蛋白（EGFP）标记的肾脏来源的Hoechst(low)细胞静脉注射到野生型成年大鼠体内时，在肾脏中未检测到EGFP(+)细胞，但在骨骼肌、肝细胞和骨髓细胞中观察到了EGFP(+)细胞。即使在诱导实验性肾小球肾炎和庆大霉素诱导的肾病后，分别促进骨髓来源的细胞分化为系膜细胞和肾小管组成细胞，但仍未观察到EGFP(+)系膜或肾小管细胞。在我们建立的从粗骨髓培养物中产生系膜样细胞的体外系统中，Hoechst(low)细胞也未产生系膜样细胞。
这些发现表明，肾脏中的Hoechst(low)细胞可能具有造血和非造血谱系的潜能，但不是肾细胞，尤其是系膜细胞和肾小管细胞的干细胞。
