Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks

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• 作者：Paul Pang¹ ; Molly Abbott¹ ; Steven L. Chang² ; Malyun Abdi¹ ; Nikita Chauhan¹ ; Murti Mistri¹ ; Joshua Ghofrani¹ ; Quynh-Anh Fucci¹ ; Colleen Walker¹ ; Corey Leonardi¹ ; Samuel Grady¹ ; Arvin Halim⁵ ; Ryan Hoffman⁶ ; Tzongshi Lu⁵ ; Huixia Cao⁵ ; Stefan G. Tullius³ ; Sayeed Malek³ ; Sanjaya Kumar³ ; Graeme Steele² ; Adam Kibel² ; Benjamin S. Freedman⁴ ; Sushrut S. Waikar¹ ; Andrew M. Siedlecki¹ ; ^{asiedlecki@bwh.harvard.edu}
• 关键词：acute kidney injury ; endothelium ; hyperfiltration ; ischemia reperfusion ; stem cell
• 刊名：Kidney International
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：91
• 期：1
• 页码：129-143
• 全文大小：5041 K
• 卷排序：91

文摘

Vascular progenitor cells show promise for the treatment of microvasculature endothelial injury. We investigated the function of renal artery progenitor cells derived from radical nephrectomy patients, in animal models of acute ischemic and hyperperfusion injuries. Present in human adventitia, CD34positive/CD105negative cells were clonal and expressed transcription factors Sox2/Oct4 as well as surface markers CXCR4 (CD184)/KDR(CD309) consistent with endothelial progenitor cells. Termed renal artery-derived vascular progenitor cells (RAPC), injected cells were associated with decreased serum creatinine after ischemia/reperfusion, reduced albuminuria after hyperperfusion, and improved blood flow in both models. A small population of RAPC integrated with the renal microvasculature following either experimental injury. At a cellular level, RAPC promoted local endothelial migration in co-culture. Profiling of RAPC microRNA identified high levels of miRNA 218; also found at high levels in exosomes isolated from RAPC conditioned media after cell contact for 24 hours. After hydrogen peroxide-induced endothelial injury, RAPC exosomes harbored Robo-1 transcript; a gene known to be regulated by mir218. Such exosomes enhanced endothelial cell migration in culture in the absence of RAPC. Thus, our work shows the feasibility of pre-emptive pro-angiogenic progenitor cell procurement from a targeted patient population and potential therapeutic use in the form of autologous cell transplantation.