Abstract
Acute kidney injury constitutes a syndrome responsible by a major percentage of acute kidney failures and it continues being associated to high mortality rates. Induced mainly by ischemia-reperfusion injury and nephrotoxic drugs, this condition is marked by a decrease in organ function and histopathological pattern of acute tubular necrosis. In search of more efficient therapies, a great deal of attention has been given to the therapeutic use of stem cells to treat kidney injuries. Bone marrow stem cells in particular have received a great attention due to its immunomodulatory properties, and its therapeutic mechanisms are intensely being studied in the literature. Purpose: In view of recent findings, the aim of our research was to get a better understanding on the potential role of bone marrow mesenchymal stem cells in a murine model of acute nephotoxicity induced by folic acid. Methods: C57Bl/6j mice (8 weeks) were submitted to acute kidney injury by folic acid (200mg/kg) administered intraperitoneally. After 24 hours, mice received mesenchymal stem cells (5.105 cells per animal) through retro-orbital intravenous injection. Mice were sacrificed after 24 hours and blood and kidneys were harvested for analysis. Results: Stem cell treatment conferred functional improvement seen through lower creatinine and urea serum levels in 8 week old C57Bl/6j mice in comparison to mice treated only with folic acid (200mg/kg body weight). This amelioration are also correlated to down regulation of kidney pro-inflammatory cytokine mRNA levels as TNF-a, IL-6 and IL-1b in stem cell treated mice. In addition, treated mice demonstrated higher levels of immunostaining for proliferating cell nuclear antigen and a tendency towards a higher Bcl-2/Bax mRNA ratio, indicating higher tissue regeneration and protection against injury-induced apoptosis. Conclusion: These results indicate bone marrow stem cells as an efficient tool in nephrotoxic kidney injury treatment.
Highlights
Despite the advancements in replacement therapies and transplant research, acute kidney injury (AKI) is still associated to high hospital mortality rates, and a high index of consequent chronic kidney disease.[1]
Kidney Function and acute tubular necrosis (ATN): In order to evaluate AKI in FA-induced nephropathy, doseresponse and time-response curves were established through kidney function analyses
Initial function assays demonstrated that bone marrowderived mesenchymal stem cells (BMSC) treatment 24h after AKI induction (FA+BMSC) conferred significant protection (p
Summary
Despite the advancements in replacement therapies and transplant research, acute kidney injury (AKI) is still associated to high hospital mortality rates (approximately 50 % of all AKI patients in intensive care units), and a high index of consequent chronic kidney disease.[1]. Studies have long focused in immunoregulatory strategies to decrease kidney inflammation and restore organ homeostasis. In the past two decades, especial attention has been given to particular therapeutic properties of stem cells. Defined according to its pluripotency and location of origin; along with its regenerative capacity, an important characteristic found in these cells has been its immunomodulatory ability. Many studies have demonstrated a special role for bone marrowderived mesenchymal stem cells (BMSC) in regulating injuries of inflammatory origin, mainly through paracrine pathways.[2, 3]
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