Comparison of Therapeutic Effects of Adipose- and Bone Marrow-Derived Mesenchymal Stem Cells on Renal Fibrosis

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Background: Mesenchymal stem cells (MSCs) have garnered strong interest as a therapeutic tool for renal fibrosis. Although both adipose-derived and bone marrowderived MSCs (ADSCs and BMSCs, respectively) suppress renal fibrosis, which of these two has a stronger therapeutic effect remains unclear. This study aimed to compare the antifibrotic effects of ADSCs and BMSCs from the same rats. Methods: ADSCs and BMSCs were extracted from adipose tissue and bone marrow from same rats and cultured in serum-containing and serum-free medium, respectively. After renal ischemia-reperfusion injury, ADSCs and BMSCs were injected through the abdominal aorta. At 21 days post-injection, the rats were sacrificed, and their kidneys were analyzed. Next, ADSCs and BMSCs were infused into mice via tail vein, and 24h survival rate and pulmonary emboli were analyzed. In in vitro experiments, we compared the procoagulation factors and humoral factors in ADSCs and BMSCs. Results: When cultured in serum-containing medium, ADSCs had a more potent inhibitory effect than BMSCs on renal fibrosis induced by ischemia-reperfusion injury in rats. ADSCs and BMSCs cultured in serum-free medium were equally effective in suppressing renal fibrosis. Mice infused with ADSCs (serum-containing or serum-free cultivation) had a higher death rate from pulmonary embolism than those infused with BMSCs. In vitro, mRNA levels of tissue factor, tumor necrosis factor-α-induced protein 6 and prostaglandin E synthase were higher in ADSCs than BMSCs, while that of vascular endothelial growth factor was higher in BMSCs than ADSCs. Although ADSCs had a stronger antifibrotic effect, these findings support the consideration of thromboembolism risk in clinical applications. Conclusions: Our results emphasize the importance of deciding between ADSCs and BMSCs based upon the target disease and culture method. Funding: Government Support - Non-U.S.

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