Collett Jason A, Traktuev Dmitry O, Mehrotra Purvi, Crone Allison, Merfeld-Clauss Stephanie, March Keith L, Basile David P
Department of Cellular and Integrative Physiology, Krannert Institute of Cardiology, Indiana University School of Medicine, Indiana Center for Vascular Biology and Medicine, Indianapolis, IN, USA.
VA Center for Regenerative Medicine Indianapolis, Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA.
J Cell Mol Med. 2017 Jul;21(7):1420-1430. doi: 10.1111/jcmm.13071. Epub 2017 Apr 28.
Damage to endothelial cells contributes to acute kidney injury (AKI) by causing impaired perfusion, while the permanent loss of the capillary network following AKI has been suggested to promote chronic kidney disease. Therefore, strategies to protect renal vasculature may impact both short-term recovery and long-term functional preservation post-AKI. Human adipose stromal cells (hASCs) possess pro-angiogenic and anti-inflammatory properties and therefore have been tested as a therapeutic agent to treat ischaemic conditions. This study evaluated hASC potential to facilitate recovery from AKI with specific attention to capillary preservation and inflammation. Male Sprague Dawley rats were subjected to bilateral ischaemia/reperfusion and allowed to recover for either two or seven days. At the time of reperfusion, hASCs or vehicle was injected into the suprarenal abdominal aorta. hASC-treated rats had significantly greater survival compared to vehicle-treated rats (88.7% versus 69.3%). hASC treatment showed hastened recovery as demonstrated by lower creatinine levels at 48 hrs, while tubular damage was significantly reduced at 48 hrs. hASC treatment resulted in a significant decrease in total T cell and Th17 cell infiltration into injured kidneys at 2 days post-AKI, but an increase in accumulation of regulatory T cells. By day 7, hASC-treated rats showed significantly attenuated capillary rarefaction in the cortex (15% versus 5%) and outer medulla (36% versus 18%) compared to vehicle-treated rats as well as reduced accumulation of interstitial alpha-smooth muscle actin-positive myofibroblasts. These results suggest for the first time that hASCs improve recovery from I/R-induced injury by mechanisms that contribute to decrease in inflammation and preservation of peritubular capillaries.
内皮细胞损伤通过导致灌注受损而促成急性肾损伤(AKI),而AKI后毛细血管网络的永久性丧失被认为会促进慢性肾病。因此,保护肾血管系统的策略可能会影响AKI后的短期恢复和长期功能维持。人脂肪基质细胞(hASC)具有促血管生成和抗炎特性,因此已作为治疗缺血性疾病的治疗剂进行了测试。本研究评估了hASC促进AKI恢复的潜力,特别关注毛细血管的保留和炎症。对雄性Sprague Dawley大鼠进行双侧缺血/再灌注,并使其恢复2天或7天。在再灌注时,将hASC或赋形剂注入肾上腺上方的腹主动脉。与赋形剂处理的大鼠相比,hASC处理的大鼠存活率显著更高(88.7%对69.3%)。hASC治疗显示出恢复加快,48小时时肌酐水平较低证明了这一点,而48小时时肾小管损伤显著减少。hASC治疗导致AKI后2天损伤肾脏中总T细胞和Th17细胞浸润显著减少,但调节性T细胞的积累增加。到第7天,与赋形剂处理的大鼠相比,hASC处理的大鼠皮质(15%对5%)和外髓质(36%对18%)的毛细血管稀疏显著减轻,间质α-平滑肌肌动蛋白阳性肌成纤维细胞的积累也减少。这些结果首次表明,hASC通过有助于减少炎症和保留肾小管周围毛细血管的机制改善了缺血/再灌注诱导损伤的恢复。
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