Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks.
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.
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Paul
P
Pang
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Molly
M
Abbott
Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Steven L
SL
Chang
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Malyun
M
Abdi
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nikita
N
Chauhan
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Murti
M
Mistri
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Joshua
J
Ghofrani
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Quynh-Anh
QA
Fucci
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Colleen
C
Walker
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Corey
C
Leonardi
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Samuel
S
Grady
Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Arvin
A
Halim
Internal Medicine, Touro College of Osteopathic Medicine, New York, NY, USA.
Ryan
R
Hoffman
Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tzongshi
T
Lu
Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Huixia
H
Cao
Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Stefan G
SG
Tullius
Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sayeed
S
Malek
Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sanjaya
S
Kumar
Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Graeme
G
Steele
Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Adam
A
Kibel
Department of Medicine, University of Washington, Seattle, Washington, USA.
Benjamin S
BS
Freedman
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sushrut S
SS
Waikar
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: asiedlecki@bwh.harvard.edu.
Andrew M
AM
Siedlecki
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000628:therapy*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002196:Capillaries / Q000473:pathology / Q000502:physiology*; D002465:Cell Movement; D018920:Coculture Techniques; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D000071063:Endoglin / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D055354:Exosomes / Q000378:metabolism; D005240:Feasibility Studies; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012077:Renal Artery / Q000166:cytology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism*; D014182:Transplantation, Autologous / Q000379:methods; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing; D000097905:Roundabout Proteins
D018952:Antigens, CD34; D003404:Creatinine; D000071063:Endoglin; D006861:Hydrogen Peroxide; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D019718:Receptors, CXCR4; D011971:Receptors, Immunologic; D040301:Vascular Endothelial Growth Factor Receptor-2; D000097905:Roundabout Proteins; C527276:CXCR4 protein, human; C547471:MIRN218 microRNA, human; C000588866:KDR protein, human
acute kidney injury; endothelium; hyperfiltration; ischemia reperfusion; stem cell
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