title: Combined endovascular coiling and intra-aneurysmal allogeneic mesenchymal stromal cell therapy for intracranial aneurysms in a rabbit model: a proof-of-concept study.
abstract: OBJECTIVE
  To assess the feasibility and efficacy of clinically translatable adjuvant mesenchymal stem/stromal cells (MSCs) therapy in improving the healing of coiled aneurysms in a rabbit elastase aneurysm model.
  
  
  METHODS
  Bone marrow-derived MSC populations were isolated from three rabbit donors in a serum-free environment and independently characterized to confirm their identity. Elastase-induced carotid aneurysms were created in nine New Zealand white rabbits. Each animal received one of the following treatments based on previous randomization: (1) coiling alone (control group); (2) coiling with an intra-aneurysmal injection of saline (vehicle group); and (3) coiling with an intra-aneurysmal injection of 5 million allogeneic MSCs (treatment group). The animals were followed for 4 weeks post-treatment, at the end of which blinded analyses of angiograms and histology were performed.
  
  
  RESULTS
  Histological results in the treatment group showed improvements over the control and vehicle groups, although the improvement over the vehicle group was not significant. Intra-aneurysmal cell therapy with 5 million allogeneic MSCs did not result in any major adverse events. Angiographic results did not show any significant difference among groups.
  
  
  CONCLUSIONS
  This proof-of-concept study shows that adjuvant MSC therapy for intracranial aneurysms is feasible and may enhance histological improvement of coiled aneurysms at 4 weeks post-treatment.
authors.affiliation: Pharmaceutical Production Research Facility (PPRF), Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Amin
authors.identifier: http://orcid.org/0000-0003-2748-4781
authors.initials: A
authors.lastname: Adibi
authors.affiliation: Department of Clinical Neurosciences, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Muneer
authors.initials: M
authors.lastname: Eesa
authors.affiliation: Department of Clinical Neurosciences, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: John H
authors.initials: JH
authors.lastname: Wong
authors.affiliation: Pharmaceutical Production Research Facility (PPRF), Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Arindom
authors.identifier: http://orcid.org/0000-0002-8994-8601
authors.initials: A
authors.lastname: Sen
authors.affiliation: Department of Clinical Neurosciences, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Alim P
authors.identifier: http://orcid.org/0000-0001-7157-5969
authors.initials: AP
authors.lastname: Mitha
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods; D057510:Endovascular Procedures / Q000379:methods*; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D010196:Pancreatic Elastase / Q000008:administration & dosage; D000075082:Proof of Concept Study; D011817:Rabbits
chemical_list: D010196:Pancreatic Elastase
keywords: Aneurysm; Bioactive; Coil; Complication; Vessel Wall