Human marrow-derived mesenchymal stromal cells decrease cisplatin renotoxicity in vitro and in vivo and enhance...

Area of Science:

• Nephrology
• Regenerative Medicine
• Cell Therapy

Background:

• Acute kidney injury (AKI) is a significant clinical challenge, often exacerbated by nephrotoxic chemotherapeutic agents like cisplatin.
• Bone marrow-derived mesenchymal stromal cells (MSCs) possess paracrine properties with therapeutic potential in various diseases.
• The protective mechanisms of MSCs in the context of chemotherapy-induced AKI require further elucidation.

Purpose of the Study:

• To investigate the in vitro effects of human MSCs (hMSCs) secretome on cisplatin-induced kidney cell damage.
• To evaluate the in vivo efficacy of intraperitoneally administered hMSCs in a murine model of cisplatin-induced AKI.

Main Methods:

• In vitro: HK-2 human proximal tubular cells were treated with cisplatin and hMSC-conditioned media.
• In vivo: NOD-SCID mice received cisplatin and subsequently hMSC intraperitoneal (ip) implantation.
• Analysis included cell viability assays, biochemical markers (blood urea nitrogen, phosphorous, amylase), cytokine profiling, immunohistochemistry, and PCR.

Main Results:

• hMSC-conditioned media enhanced cisplatin-treated HK-2 cell survival in vitro, associated with increased phosphorylated Akt (p-Akt) and VEGF signaling.
• In vivo, ip hMSC administration significantly improved kidney function, reduced blood urea nitrogen, phosphorous, and amylase levels, and increased survival rates in mice with AKI.
• hMSCs decreased plasma inflammatory cytokines, reduced kidney cell apoptosis, promoted proliferation, and were detected in mouse kidneys with enhanced p-Akt expression.

Conclusions:

• hMSCs exert significant prosurvival effects on renal cells both in vitro and in vivo.
• Intraperitoneal delivery of hMSCs demonstrates paracrine kidney-protective capabilities, suggesting a role for secreted factors.
• These findings support the potential clinical application of hMSCs for managing acute kidney injury.