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

Kidney Int. 2017 Jan;91(1):129-143. doi: 10.1016/j.kint.2016.07.037. Epub 2016 Sep 29.

Abstract

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.

Keywords: acute kidney injury; endothelium; hyperfiltration; ischemia reperfusion; stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / therapy*
  • Animals
  • Antigens, CD34 / metabolism
  • Capillaries / pathology
  • Capillaries / physiology*
  • Cell Movement
  • Coculture Techniques
  • Creatinine / blood
  • Disease Models, Animal
  • Endoglin / metabolism
  • Endothelium / cytology
  • Exosomes / metabolism
  • Feasibility Studies
  • Humans
  • Hydrogen Peroxide / toxicity
  • Kidney / blood supply
  • Kidney / pathology*
  • Mice
  • MicroRNAs / metabolism
  • Nerve Tissue Proteins / metabolism
  • Receptors, CXCR4 / metabolism
  • Receptors, Immunologic / metabolism
  • Renal Artery / cytology
  • Stem Cell Transplantation / methods*
  • Stem Cells / metabolism*
  • Transplantation, Autologous / methods
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Wound Healing*

Substances

  • Antigens, CD34
  • CXCR4 protein, human
  • Endoglin
  • MIRN218 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • Receptors, CXCR4
  • Receptors, Immunologic
  • roundabout protein
  • Creatinine
  • Hydrogen Peroxide
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2