title: Unexpected calcification after direct intravascular injection of autologous bone marrow-derived cells in a chronic total occlusion model.
abstract: OBJECTIVE
  Patients with symptomatic chronic total occlusions (CTO) remain a therapeutic challenge. Enhancement of intraluminal neovascularisation by pro-angiogenic therapies has been proposed as a new strategy to improve percutaneous revascularisation. The aim of this study was to investigate the effects of intraluminal injection of bone marrow-derived cells (BMC) into experimental CTO.
  
  
  RESULTS
  CTO were created in the femoral arteries of 43 New Zealand White rabbits using the thrombin injection model. At 12 weeks following CTO creation, 33 rabbits were injected with either cultured BMC (n=19) or control DMEM alone (n=14) directly into the CTO. Ten rabbits were used for cell tracking (seven BMC and three control). BMC labelled with fluorescent Qdot® nanocrystals were identified in the CTO up to one week after injection. Animals were sacrificed at three to five weeks post-treatment and arterial samples were excised for micro-CT imaging and histologic morphometric analysis. There was a significant but modest increase in neovascularisation in BMC-treated arteries compared to controls (7.47±4.75% vs. 4.35±2.97%, p<0.05). However, unexpected intravascular calcification was only detected within the CTO in BMC cell treated arteries. Western blot for conditioned medium from BMC showed up-regulation of osteogenic proteins (BMP-2 and -7).
  
  
  CONCLUSIONS
  Although direct delivery of BMC into CTO increases neovascularisation, undesirable vascular calcification will limit this therapeutic approach.
authors.affiliation: Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Nili
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lim
authors.forename: Beiping
authors.initials: B
authors.lastname: Qiang
authors.forename: Xiuling
authors.initials: X
authors.lastname: Qi
authors.forename: Max J
authors.initials: MJ
authors.lastname: Weisbrod
authors.forename: Michelle
authors.initials: M
authors.lastname: Ladouceur-Wodzak
authors.forename: Naomi
authors.initials: N
authors.lastname: Gofine
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Berk
authors.forename: Jamie
authors.initials: J
authors.lastname: Saperia
authors.forename: Graham A
authors.initials: GA
authors.lastname: Wright
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D058948:Cell Tracking; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D011817:Rabbits; D013917:Thrombin; D013997:Time Factors; D014182:Transplantation, Autologous; D061205:Vascular Calcification / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D013917:Thrombin