Do we really need “stem” cell for renal regeneration? View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-11

AUTHORS

KEIICHI HISHIKAWA

ABSTRACT

Kidney International (2005) 68, 1966–1967; doi:10.1038/ki.2005.21 Adult stem cells can be identified by a side population phenotype, but its stemness is still unclear. First, we will show that side population cells that are not derived from bone marrow reside in the renal interstitial spaces, and contribute to tissue regeneration in renal failure without transdifferentiating into damaged cells. In two different mouse chronic renal failure models, the number of side population cells is reduced. However, microarray analysis (of 3800 genes) clarified that the remaining side population cells expressed high levels of molecular mediators of kidney morphogenesis and stem cell signature genes. Immunohistochemical studies using kidney side population cell specific markers (bcrp1+, Sca1+, CD45-, musculin+, CD63+) showed that kidney side population cells were not part of the hematopoietic system and resided in the renal interstitial spaces. Cultured kidney side population cells could differentiate into multilineages, and these cells successfully integrated into the developing metanephros in cocultured conditions. Systemic infusion of kidney side population cells, but not direct transplantation under the kidney capsule, improved renal function in cisplatin-induced renal failure. Unexpectedly, the infused cells were found localized in interstitial spaces of healthy kidney tissue but not in damaged areas. These results show that homing of exogenous kidney side population cells into the interstitial spaces may be essential for augmenting the local regeneration system. Second, we will show some results of pharmacological intervention targeting adult stem-like cells in kidney. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are hallmark of many diseases such cancer, and several histone deacetylase inhibitors (HDACIs) are used for cancer therapy but adult stem cells can be good targets of HDACIs for pharamacologic regenerative medicine. In this study, we examined whether Trichostatin A (TSA) prevents progression of chronic renal failure by activating adult stem-like cells in kidney. As a chronic renal failure model, we used nephrotoxic serum nephritis in C57BL/6 mice. Adult stem like cells were analyzed and sorted by fluorescence-activated cell sorter (FACS) with Hoechst 33342 staining as side population cells. Daily injection of TSA significantly reduced urinary protein excretion and improved glomerular score by hitopathologic examination. TSA also increased expression of renoprotective genes such as bone morphogenetic protein-7 (BMP-7), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in kidney side population cells but not in nonside population cells suggesting that side population cells are good target for HDACIs. Taken together, existence of stem cell in kidney remains to be definitely determined, but adult stem-like cells such as side population cells are good target for renal regeneration by cell therapy and pharmacologic intervention. More... »

PAGES

1966-1967

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ki.2005.21

DOI

http://dx.doi.org/10.1038/ki.2005.21

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040866366


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