title: Pilot safety study of perivascular injection of tissue-engineered allogeneic aortic endothelial cells in patients undergoing minimally invasive peripheral revascularization.
abstract: OBJECTIVE
  Restenosis is a limitation of endovascular interventions performed in the superficial femoral artery (SFA). Preclinical studies have demonstrated that the perivascular delivery of tissue-engineered allogeneic aortic endothelial cells (PVS-10200) reduced stenosis in porcine models of SFA revascularization. The purpose of this study was to investigate the safety and feasibility of percutaneous PVS-10200 delivery after angioplasty and stenting in the SFA of patients with peripheral artery disease.
  
  
  METHODS
  In this phase I open-label trial, 21 patients (average lesion length of 10.10 ± 2.36 cm and ≥70% stenosis) were treated with PVS-10200: 11 in a low-dose cohort (cohort A) and 10 in a high-dose cohort (cohort B). The primary objective was to demonstrate the safety (incidence of major adverse events) of PVS-10200 within 4 weeks after surgery. Secondary end points included assessments of resting ankle-brachial index (ABI) in the treated leg, Fontaine class, and time to target lesion revascularization (TLR).
  
  
  RESULTS
  No patient had a major adverse event within 4 weeks. One patient required a limb amputation at 30 weeks. At 48 weeks, cohort A and cohort B patients maintained a 37% and 62% increase in ABI compared with baseline, respectively; 70% of cohort A and 78% of cohort B improved by ≥1 Fontaine classification stage, and the TLR rate was 39% for cohort A and 20% for cohort B.
  
  
  CONCLUSIONS
  Percutaneous local delivery of PVS-10200 is a well-tolerated and novel therapeutic approach that may be a suitable treatment for patients after endovascular intervention of the SFA. Larger randomized trials are needed to determine if PVS-10200 can improve ABI and reduce TLR rates.
authors.affiliation: Department of Vascular Medicine, South Hospital, Amiens, France.
authors.forename: Marie-Antoinette
authors.initials: MA
authors.lastname: Sevestre
authors.affiliation: AP-HP, Saint-Louis Hospital, Cell Therapy Unit and Clinical Investigation in Biotherapies (CBT501), Paris Diderot Sorbonne Paris Cité University, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghero
authors.affiliation: AP-HP, Bichat-Claude-Bernard Hospital, Department of Vascular, Thoracic, and Lung Transplantation, Paris.
authors.forename: Yves
authors.initials: Y
authors.lastname: Castier
authors.affiliation: Pervasis Therapeutics, Cambridge, Mass.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Nugent
authors.affiliation: Shire, San Diego, Calif.
authors.forename: Sophie
authors.initials: S
authors.lastname: Visonneau
authors.affiliation: AP-HP, Department of Vascular Surgery, Georges Pompidou European Hospital, René Descartes Paris 5 University, Paris, France. Electronic address: jean-marc.alsac@egp.aphp.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alsac
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D001013:Aorta, Thoracic / Q000166:cytology*; D001157:Arterial Occlusive Diseases / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000601:surgery*; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007267:Injections; D008297:Male; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures / Q000379:methods*; D010865:Pilot Projects; D011183:Postoperative Complications / Q000453:epidemiology; D011446:Prospective Studies; D011859:Radiography; D023822:Tissue Engineering; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex; D014654:Vascular Patency