Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan 466-8550.
Cell Transplant. 2013;22(2):287-97. doi: 10.3727/096368912X655019. Epub 2012 Sep 7.
Current studies suggest that mesenchymal stromal cells (MSCs) improve acute kidney injury (AKI) via paracrine/endocrine effects. We established human adipose tissue-derived stromal cells (hASCs) cultured in low (2%) serum (hLASCs), which have great potential of tissue regeneration. The present study was performed to investigate the therapeutic effects of hLASCs on AKI and to clarify the mechanisms involved. In low serum, hASCs proliferated well, while human bone marrow-derived stromal cells (hBMSCs) did not. hLASCs secreted higher levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) than did hASCs cultured in high (20%) serum (hHASCs) or hBMSCs cultured in high serum (hHBMSCs). AKI was induced in nude rats by folic acid, and hLASCs, hHASCs or control medium were administered into the renal subcapsules. hLASCs significantly attenuated acute renal damage, while hHASCs showed far less effect. Furthermore, interstitial fibrosis observed on day 14 was less pronounced in the hLASCs group. Cell tracking experiment showed no evidence of transdifferentiation. Intravenous injection of hLASCs or hHBMSCs or subcapsular injection of hHBMSCs did not ameliorate AKI. Concerning the mechanisms, our in vivo experiments showed that HGF knockdown by siRNA impaired the ability of hLASCs to protect the kidney from acute injury whereas VEGF knockdown did not. In conclusion, hLASCs, but not hHASCs or hHBMSCs, ameliorated AKI via paracrine effects, and HGF is one of the key mediators.
目前的研究表明，间充质基质细胞（MSCs）通过旁分泌/内分泌作用改善急性肾损伤（AKI）。我们建立了在低（2%）血清中培养的人脂肪组织来源基质细胞（hASCs）（hLASCs），其具有很大的组织再生潜力。本研究旨在探讨 hLASCs 对 AKI 的治疗作用，并阐明其相关机制。在低血清中，hASCs 增殖良好，而人骨髓基质细胞（hBMSCs）则不行。与高（20%）血清中培养的 hASCs（hHASCs）或高血清中培养的 hBMSCs（hHBMSCs）相比，hLASCs 分泌更高水平的肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）。通过叶酸诱导裸鼠 AKI，并将 hLASCs、hHASCs 或对照培养基注入肾被膜下。hLASCs 显著减轻急性肾损伤，而 hHASCs 作用较小。此外，hLASCs 组第 14 天观察到的间质纤维化程度较轻。细胞追踪实验未发现转分化的证据。静脉注射 hLASCs 或 hHBMSCs 或肾被膜下注射 hHBMSCs 均不能改善 AKI。关于机制，我们的体内实验表明，siRNA 敲低 HGF 会损害 hLASCs 保护肾脏免受急性损伤的能力，而敲低 VEGF 则不会。总之，hLASCs 而非 hHASCs 或 hHBMSCs 通过旁分泌作用改善 AKI，HGF 是其中一个关键介质。
