Unexpected calcification after direct intravascular injection of autologous bone marrow-derived cells in a chronic total occlusion model

Nafiseh Nili, Sang Yeob Lim, Beiping Qiang, Xiuling Qi, Max J. Weisbrod, Michelle Ladouceur-Wodzak, Naomi Gofine, Thomas A. Berk, Jamie Saperia, Graham A. Wright, Bradley H. Strauss

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Abstract

Aims: 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. Methods and 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.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalEuroIntervention
Volume10
Issue number3
DOIs
Publication statusPublished - 2014 Jan 1

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nili, N., Lim, S. Y., Qiang, B., Qi, X., Weisbrod, M. J., Ladouceur-Wodzak, M., Gofine, N., Berk, T. A., Saperia, J., Wright, G. A., & Strauss, B. H. (2014). Unexpected calcification after direct intravascular injection of autologous bone marrow-derived cells in a chronic total occlusion model. EuroIntervention, 10(3), 329-336. https://doi.org/10.4244/EIJV10I3A56