PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Adipose Stromal Cells-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay Between Proximal Tubular Epithelial Cells and Macrophages
Rendra, E.; Uhlig, S.; Moskal, I.; Thielemann, C.; Klüter, H.; Bieback, K. Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells2024, 13, 121.
Rendra, E.; Uhlig, S.; Moskal, I.; Thielemann, C.; Klüter, H.; Bieback, K. Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells 2024, 13, 121.
Rendra, E.; Uhlig, S.; Moskal, I.; Thielemann, C.; Klüter, H.; Bieback, K. Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells2024, 13, 121.
Rendra, E.; Uhlig, S.; Moskal, I.; Thielemann, C.; Klüter, H.; Bieback, K. Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages. Cells 2024, 13, 121.
Abstract
(1) Background: The chemotherapeutic drug cisplatin exerts toxic side effects causing acute kidney injury. Mesenchymal stromal cells can ameliorate cisplatin-induced kidney injury. We hypothe-size that the MSC secretome orchestrates the vicious cycle of injury and inflammation by acting on proximal tubule epithelial cells (PTECs) and macrophages individually, but further by coun-teracting their cellular crosstalk. (2) Methods: Conditioned medium (CM) from adipose stromal cells was used, first assessing its effect on cisplatin injury in PTECs. Second, effects of cisplatin and CM on macrophages were measured. Lastly, in an indirect co-culture system the interplay between the two cell types was assessed. (3) Results: First, CM rescued PTECs from cisplatin-induced apoptosis by reducing oxidative stress and expression of nephrotoxicity genes. Second, while cisplatin exerted only minor effects on macrophages, CM skewed macrophage phenotypes to the anti-inflammatory M2-like phenotype and increased phagocytosis. Finally, in the co-culture system, CM suppressed PTEC death by inhibiting apoptosis and nuclei fragmentation. CM lowered TNF-α release. While cisplatin inhibited macrophage phagocytosis, PTECs, and CM to a greater extent, enhanced it. CM strongly dampened the inflammatory macrophage cytokine secretion triggered by PTECs. (4) Conclusion: ASC-CM surpasses the PTEC-macrophage cross-talk in cisplatin injury. The positive effects on reducing cisplatin cytotoxicity, on polarizing mac-rophages and on fine-tuning cytokine secretion underscores MSCs CM benefit to prevent kidney injury progression.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
