Mouse kidney progenitor cells accelerate renal regeneration and prolong survival after ischemic injury.
Acute tubular necrosis is followed by regeneration of damaged renal tubular epithelial cells, and renal stem cells are supposed to contribute to this process. The purpose of our study is to test the hypothesis that renal stem cells isolated from adult mouse kidney accelerate renal regeneration via participation in the repair process. A unique population of cells exhibiting characteristics consistent with renal stem cells, mouse kidney progenitor cells (MKPC), was isolated from Myh9 targeted mutant mice. Features of these cells include (1) spindle-shaped morphology, (2) self-renewal of more than 100 passages without evidence of senescence, and (3) expression of Oct-4, Pax-2, Wnt-4, WT-1, vimentin, alpha-smooth muscle actin, CD29, and S100A4 but no SSEA-1, c-kit, or other markers of more differentiated cells. MKPC exhibit plasticity as demonstrated by the ability to differentiate into endothelial cells and osteoblasts in vitro and endothelial cells and tubular epithelial cells in vivo. The origin of the isolated MKPC was from the interstitium of medulla and papilla. Importantly, intrarenal injection of MKPC in mice with ischemic injury rescued renal damage, as manifested by decreases in peak serum urea nitrogen, the infarct zone, and the necrotic injury. Seven days after the injury, some MKPC formed vessels with red blood cells inside and some incorporated into renal tubules. In addition, MKPC treatment reduces the mortality in mice after ischemic injury. Our results indicate that MKPC represent a multipotent adult stem cell population, which may contribute to the renal repair and prolong survival after ischemic injury.
Lee
Po-Tsang
PT
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lin
Hsi-Hui
HH
Jiang
Si-Tse
ST
Lu
Pei-Jung
PJ
Chou
Kang-Ju
KJ
Fang
Hua-Chang
HC
Chiou
Yuan-Yow
YY
Tang
Ming-Jer
MJ
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007238:Infarction / Q000503:physiopathology / Q000601:surgery; D007511:Ischemia / Q000503:physiopathology / Q000601:surgery*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology / Q000601:surgery*; D007674:Kidney Diseases / Q000503:physiopathology / Q000601:surgery*; D007684:Kidney Tubules / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D020127:Recovery of Function / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome
D015415:Biomarkers