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

Autor: Pang P; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Abbott M; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chang SL; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Abdi M; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chauhan N; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Mistri M; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Ghofrani J; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Fucci QA; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Walker C; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Leonardi C; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Grady S; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Halim A; Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Hoffman R; Internal Medicine, Touro College of Osteopathic Medicine, New York, NY, USA., Lu T; Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Cao H; Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Tullius SG; Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Malek S; Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kumar S; Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Steele G; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kibel A; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Freedman BS; Department of Medicine, University of Washington, Seattle, Washington, USA., Waikar SS; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Siedlecki AM; Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: asiedlecki@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Kidney international [Kidney Int] 2017 Jan; Vol. 91 (1), pp. 129-143. Date of Electronic Publication: 2016 Sep 29.
DOI: 10.1016/j.kint.2016.07.037
Abstrakt: 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.
(Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE