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.
Highlights
Acute renal failure (ARF) is characterized by rapidly declining renal functions induced by toxic or ischemic damage of renal tubular and vascular cells with a key role of inflammation in the pathophysiology of the disease
The present study shows that culture expanded fetal kidney cells express mesenchymal and renal progenitor markers
To the best of our knowledge this represents the first study in literature on the therapeutic effects and mechanism of action of in vitro expanded fetal kidney cells in an animal model of ischemic ARF
Summary
Acute renal failure (ARF) is characterized by rapidly declining renal functions induced by toxic or ischemic damage of renal tubular and vascular cells with a key role of inflammation in the pathophysiology of the disease. It is a global disease increasingly affecting people of all age PLOS ONE | DOI:10.1371/journal.pone.0131057. Therapeutic Effects of Fetal Kidney Cells in Acute Renal Failure groups and having a high mortality rate. Cell therapy represents a potential new therapeutic approach for ARF as stem cells may simultaneously target the key manifestations of ARF including renal vascular damage and inflammation [3, 4]. A suitable renogenic cell type to obtain a clinically relevant therapeutic effect in ARF has not yet been achieved and no cell based clinical therapy has yet been established
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
