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Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

Gupta AK, Jadhav SH, Tripathy NK, Nityanand S - PLoS ONE (2015)

Bottom Line: Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all).The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both).In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all).

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Research Facility (SCRF), Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India.

ABSTRACT
Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all). The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both). In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all). Our data shows that culture expanded fetal kidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

No MeSH data available.


Related in: MedlinePlus

In vivo tracking of PKH26 positive cells in IR induced damaged kidney.Representative immunoflourescence photomicrographs (40X) of fetal kidney cells treated kidney showing (A) CK 19, green (B) Hoechst, blue (C) PKH26 labeled cells, red, located in the interstitial spaces and peri-tubular areas of the kidney (D) Overlay of images of (A), (B) and (C). (E) Overlay of images of (A) and (B). (F) Overlay of images of (B) and (C).
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pone.0131057.g005: In vivo tracking of PKH26 positive cells in IR induced damaged kidney.Representative immunoflourescence photomicrographs (40X) of fetal kidney cells treated kidney showing (A) CK 19, green (B) Hoechst, blue (C) PKH26 labeled cells, red, located in the interstitial spaces and peri-tubular areas of the kidney (D) Overlay of images of (A), (B) and (C). (E) Overlay of images of (A) and (B). (F) Overlay of images of (B) and (C).

Mentions: The ARF rats infused with PKH 26 labeled fetal kidney cells were sacrificed 72 hours after cell administration and sections of damaged kidneys were examined by fluorescent microscopy. The kidney sections were observed to have 8.28±1.27 PKH26 positive cells/HPF and these cells were found to be localized in the interstitial spaces and peri-tubular areas of the kidney. The tubules stained positive for CK 19 (Fig 5A–5F).


Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

Gupta AK, Jadhav SH, Tripathy NK, Nityanand S - PLoS ONE (2015)

In vivo tracking of PKH26 positive cells in IR induced damaged kidney.Representative immunoflourescence photomicrographs (40X) of fetal kidney cells treated kidney showing (A) CK 19, green (B) Hoechst, blue (C) PKH26 labeled cells, red, located in the interstitial spaces and peri-tubular areas of the kidney (D) Overlay of images of (A), (B) and (C). (E) Overlay of images of (A) and (B). (F) Overlay of images of (B) and (C).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4472721&req=5

pone.0131057.g005: In vivo tracking of PKH26 positive cells in IR induced damaged kidney.Representative immunoflourescence photomicrographs (40X) of fetal kidney cells treated kidney showing (A) CK 19, green (B) Hoechst, blue (C) PKH26 labeled cells, red, located in the interstitial spaces and peri-tubular areas of the kidney (D) Overlay of images of (A), (B) and (C). (E) Overlay of images of (A) and (B). (F) Overlay of images of (B) and (C).
Mentions: The ARF rats infused with PKH 26 labeled fetal kidney cells were sacrificed 72 hours after cell administration and sections of damaged kidneys were examined by fluorescent microscopy. The kidney sections were observed to have 8.28±1.27 PKH26 positive cells/HPF and these cells were found to be localized in the interstitial spaces and peri-tubular areas of the kidney. The tubules stained positive for CK 19 (Fig 5A–5F).

Bottom Line: Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all).The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both).In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all).

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Research Facility (SCRF), Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India.

ABSTRACT
Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all). The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both). In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all). Our data shows that culture expanded fetal kidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

No MeSH data available.


Related in: MedlinePlus