Stem cells from foreign body granulation tissue accelerate recovery from acute kidney injury.
BACKGROUND
In previous studies, we obtained mesenchymal stem cells called granulation tissue stem cells (GTSC) from a regenerating granulation tissue created by placing a foreign body in the subcutaneous tissue of rats. Here, we used GTSC to ameliorate ischemia/reperfusion-induced acute kidney injury (AKI) in rats.


METHODS
In two groups of Fischer rats, we induced ischemia/reperfusion injury. Group 1 (treated rats) received one intravenous injection of GTSC 3 h after injury; Group 2 (control rats) received vehicle. Both groups were subsequently studied by renal function tests, kidney histology and immunohistochemistry.


RESULTS
At 24 and 48 h after injury, plasma creatinine and blood urea nitrogen were significantly lower in the treated rats as compared to control rats. The levels remained low and declined to near baseline levels by Day 4 in the treated group. At the cortico-medullary region, the treated rats showed significantly higher renal tubular cell proliferation and less tubular cell apoptosis. Histological analysis of the kidney for tubular dilatation, necrosis, congestion and casts was not significantly different in the two groups. To understand the mechanism of the GTSC effect, messenger RNA levels of several growth and immune modulatory factors were quantified in cultured GTSC and compared with those in cultured glomerular epithelial cell (GEC; a non-stem cell line). GTSC had 2- to 8-fold higher expression of FGF2, HGF, IGF-1, vascular endothelial growth factor (growth factors) and IL-4, IL-6 (anti-inflammatory factors) than GEC.


CONCLUSIONS
Administration of GTSC accelerates recovery in rats with ischemia/reperfusion-induced AKI. This effect may be mediated by the paracrine action of growth and immune-suppressive factors secreted by these cells.
Hektoen Institute of Medicine, Chicago, IL 60612, USA.
Jilpa
J
Patel
Nishit
N
Pancholi
Krishnamurthy P
KP
Gudehithlu
Perianna
P
Sethupathi
Peter D
PD
Hart
George
G
Dunea
Jose A L
JA
Arruda
Ashok K
AK
Singh
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005547:Foreign Bodies; D006097:Granulation Tissue / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D023421:Models, Animal; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000150:complications*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I; D003404:Creatinine