Document Detail


Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells.
MedLine Citation:
PMID:  16007251     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ischemia causes kidney tubular cell damage and abnormal renal function. The kidney is capable of morphological restoration of tubules and recovery of function. Recently, it has been suggested that cells repopulating the ischemically injured tubule derive from bone marrow stem cells. We studied kidney repair in chimeric mice expressing GFP or bacterial beta-gal or harboring the male Y chromosome exclusively in bone marrow-derived cells. In GFP chimeras, some interstitial cells but not tubular cells expressed GFP after ischemic injury. More than 99% of those GFP interstitial cells were leukocytes. In female mice with male bone marrow, occasional tubular cells (0.06%) appeared to be positive for the Y chromosome, but deconvolution microscopy revealed these to be artifactual. In beta-gal chimeras, some tubular cells also appeared to express beta-gal as assessed by X-gal staining, but following suppression of endogenous (mammalian) beta-gal, no tubular cells could be found that stained with X-gal after ischemic injury. Whereas there was an absence of bone marrow-derived tubular cells, many tubular cells expressed proliferating cell nuclear antigen, which is reflective of a high proliferative rate of endogenous surviving tubular cells. Upon i.v. injection of bone marrow mesenchymal stromal cells, postischemic functional renal impairment was reduced, but there was no evidence of differentiation of these cells into tubular cells of the kidney. Thus, our data indicate that bone marrow-derived cells do not make a significant contribution to the restoration of epithelial integrity after an ischemic insult. It is likely that intrinsic tubular cell proliferation accounts for functionally significant replenishment of the tubular epithelium after ischemia.
Authors:
Jeremy S Duffield; Kwon Moo Park; Li-Li Hsiao; Vicki R Kelley; David T Scadden; Takaharu Ichimura; Joseph V Bonventre
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-06-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  115     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-11     Completed Date:  2005-08-31     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1743-55     Citation Subset:  AIM; IM    
Affiliation:
Renal Division and Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Transplantation
Epithelial Cells / pathology,  physiology
Female
Green Fluorescent Proteins / genetics,  metabolism
Hematopoietic Stem Cells / pathology
Ischemia / pathology,  physiopathology
Kidney / blood supply,  injuries*,  pathology,  physiopathology
Kidney Tubules / pathology*,  physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Radiation Chimera
Recombinant Proteins / genetics,  metabolism
Regeneration
Reperfusion Injury / pathology,  physiopathology
Grant Support
ID/Acronym/Agency:
DK 38452/DK/NIDDK NIH HHS; DK 39773/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Recombinant Proteins; 0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections
Comment In:
J Clin Invest. 2005 Jul;115(7):1705-8   [PMID:  16007248 ]

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