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Updated: May 26, 2026
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Human adipose tissue-derived mesenchymal stem cells protect kidneys from cisplatin nephrotoxicity in rats
Jin Hyun Kim1, Dong Jun Park, Ji Chul Yun
1Clinical Research Institute, Gyeongsang National University Hospital, Gyeongsang National University, Gyeongnam, Republic of Korea.
Abstract:
Cisplatin has multiple cellular targets and modes of action that lead to nephrotoxicity. This suggests novel therapies that act at multiple cisplatin target sites may be effective. We tested whether human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) can affect multiple target sites and protect against cisplatin-induced kidney damage. Rats were divided into four groups: control, infused with Ad-MSCs, injected with cisplatin, and cisplatin followed by infusion of Ad-MSCs. Animal survival and renal function were decreased and histological damage was increased in cisplatin-treated rats at day 3. Infusion of Ad-MSCs ameliorated renal dysfunction and tissue injury caused by cisplatin, leading to increased survival. Apoptotic cell death in the kidney was significantly reduced by infusion of Ad-MSCs. Activation of p53, JNK, and ERK and the expression of inflammation-related molecules were also decreased in the kidney that received Ad-MSCs. Very few Ad-MSCs were detected in the kidney. Conditioned medium from cultured Ad-MSCs had renal-protective functions in vivo and in vitro. Renal dysfunction and tissue damage caused by cisplatin were significantly reduced in rats treated with Ad-MSCs-conditioned medium. The viability of cultured renal proximal tubular cells exposed to cisplatin was also improved by coculture with Ad-MSCs or with conditioned medium. Release of proinflammatory mediators induced by cisplatin was inhibited in coculture with Ad-MSCs. Our results show that human Ad-MSCs exert a paracrine-protective effect on cisplatin nephrotoxicity at multiple target sites and suggest that human Ad-MSCs might be a new therapeutic approach for patients with acute kidney injury.
Insights
Human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) protect against cisplatin-induced kidney damage by reducing apoptosis and inflammation. These stem cells offer a potential new therapy for acute kidney injury.
Area of Science:
- Nephrology
- Stem Cell Biology
- Pharmacology
Background:
- Cisplatin is a widely used chemotherapy agent with significant nephrotoxic side effects.
- The complex mechanisms of cisplatin-induced kidney damage involve multiple cellular targets.
- Novel therapeutic strategies targeting these multiple sites are needed to mitigate cisplatin nephrotoxicity.
Purpose of the Study:
- To investigate the potential of human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) in protecting against cisplatin-induced nephrotoxicity.
- To determine if Ad-MSCs can ameliorate kidney damage by acting on multiple cisplatin target sites.
- To explore the therapeutic efficacy of Ad-MSCs and their conditioned medium in a rat model of cisplatin nephrotoxicity.
Main Methods:
- Rats were assigned to control, Ad-MSC infusion, cisplatin injection, or cisplatin followed by Ad-MSC infusion groups.
- Renal function, animal survival, histological damage, and apoptosis were assessed.
- The effects of Ad-MSC conditioned medium and co-culture with Ad-MSCs on renal cells were evaluated in vitro and in vivo.
Main Results:
- Cisplatin administration significantly decreased survival, impaired renal function, and increased kidney damage and apoptosis.
- Ad-MSC infusion improved renal function, reduced tissue injury, and increased survival in cisplatin-treated rats.
- Ad-MSCs and their conditioned medium demonstrated paracrine protective effects, reducing apoptosis, inflammation, and improving renal cell viability.
Conclusions:
- Human Ad-MSCs exert a paracrine-protective effect against cisplatin nephrotoxicity by targeting multiple pathways.
- Ad-MSCs and their conditioned medium show significant therapeutic potential for mitigating cisplatin-induced acute kidney injury.
- Ad-MSCs represent a promising novel therapeutic approach for patients experiencing chemotherapy-related kidney damage.
