PMID- 16007252 OWN - NLM STAT- MEDLINE DCOM- 20050831 LR - 20220330 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 115 IP - 7 DP - 2005 Jul TI - Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. PG - 1756-64 AB - Ischemic injury to the kidney produces acute tubular necrosis and apoptosis followed by tubular regeneration and recovery of renal function. Although mitotic cells are present in the tubules of postischemic kidneys, the origins of the proliferating cells are not known. Bone marrow cells (BMCs) can differentiate across lineages to repair injured organs, including the kidney. However, the relative contribution of intrarenal cells and extrarenal cells to kidney regeneration is not clear. We produced transgenic mice that expressed enhanced GFP (EGFP) specifically and permanently in mature renal tubular epithelial cells. Following ischemia/reperfusion injury (IRI), EGFP-positive cells showed incorporation of BrdU and expression of vimentin, which provides direct evidence that the cells composing regenerating tubules are derived from renal tubular epithelial cells. In BMC-transplanted mice, 89% of proliferating epithelial cells originated from host cells, and 11% originated from donor BMCs. Twenty-eight days after IRI, the kidneys contained 8% donor-derived cells, of which 8.4% were epithelial cells, 10.6% were glomerular cells, and 81% were interstitial cells. No renal functional improvement was observed in mice that were transplanted with exogenous BMCs. These results show that intrarenal cells are the main source of renal repair, and a single injection of BMCs does not make a significant contribution to renal functional or structural recovery. FAU - Lin, Fangming AU - Lin F AD - Department of Pediatrics and Department of Internal Medicine and Division of Basic Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 5390-9063, USA. Fangming.lin@utsouthwestern.edu FAU - Moran, Ashley AU - Moran A FAU - Igarashi, Peter AU - Igarashi P LA - eng GR - K08 DK062839/DK/NIDDK NIH HHS/United States GR - R01 DK066535/DK/NIDDK NIH HHS/United States GR - DK062839/DK/NIDDK NIH HHS/United States GR - DK066535/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Recombinant Proteins) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM CIN - J Clin Invest. 115:1705. MH - Animals MH - Bone Marrow Cells/pathology MH - Bone Marrow Transplantation MH - Cell Differentiation MH - Epithelial Cells/pathology MH - Female MH - Green Fluorescent Proteins/genetics MH - In Situ Hybridization, Fluorescence MH - Kidney/injuries/*pathology/*physiology MH - Kidney Tubules/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Recombinant Proteins/genetics MH - *Regeneration MH - Reperfusion Injury/genetics/*pathology/physiopathology MH - Y Chromosome PMC - PMC1159127 EDAT- 2005/07/12 09:00 MHDA- 2005/09/01 09:00 PMCR- 2005/07/01 CRDT- 2005/07/12 09:00 PHST- 2004/08/11 00:00 [received] PHST- 2005/05/17 00:00 [accepted] PHST- 2005/07/12 09:00 [pubmed] PHST- 2005/09/01 09:00 [medline] PHST- 2005/07/12 09:00 [entrez] PHST- 2005/07/01 00:00 [pmc-release] AID - 23015 [pii] AID - 10.1172/JCI23015 [doi] PST - ppublish SO - J Clin Invest. 2005 Jul;115(7):1756-64. doi: 10.1172/JCI23015.