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

被引：35

作者：

Pang, Paul ^{[1
]}

Abbott, Molly ^{[1
]}

Chang, Steven L. ^{[2
]}

Abdi, Malyun ^{[1
]}

Chauhan, Nikita ^{[1
]}

Mistri, Murti ^{[1
]}

Ghofrani, Joshua ^{[1
]}

Quynh-Anh Fucci ^{[1
]}

Walker, Colleen ^{[1
]}

Leonard, Corey ^{[1
]}

Grady, Samuel ^{[1
]}

Halim, Arvin ^{[5
]}

Hoffman, Ryan ^{[6
]}

Lu, Tzongshi ^{[5
]}

Cao, Huixia ^{[5
]}

Tullius, Stefan G. ^{[3
]}

Malek, Sayeed ^{[3
]}

Kumar, Sanjaya ^{[3
]}

Steele, Graeme ^{[2
]}

Kibel, Adam ^{[2
]}

Freedman, Benjamin S. ^{[4
]}

Waikar, Sushrut S. ^{[1
]}

Siedlecki, Andrew M. ^{[1
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Internal Med, Boston, MA USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Urol Div, Boston, MA USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Transplant Surg Div, Boston, MA USA

[4] Univ Washington, Dept Med, Seattle, WA USA

[5] Harvard Med Sch, Brigham & Womens Hosp, Internal Med, Boston, MA USA

[6] Touro Coll Osteopath Med, Internal Med, New York, NY USA

来源：

KIDNEY INTERNATIONAL | 2017年 / 91卷 / 01期

关键词：

acute kidney injury; endothelium; hyperfiltration; ischemia reperfusion; stem cell; MESENCHYMAL STEM-CELLS; POTENTIALLY ADVERSE RESPONSE; REMNANT NEPHRONS; KIDNEY REPAIR; EXPRESSION; RECEPTOR; DISEASE; RGS4; DEFICIENCY; MICRORNAS;

D O I：

10.1016/j.kint.2016.07.037

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：129 / 143

页数：15

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