In vivo MR imaging of intraarterially delivered magnetically labeled mesenchymal stem cells in a canine stroke model

PLoS One. 2013;8(2):e54963. doi: 10.1371/journal.pone.0054963. Epub 2013 Feb 7.

Abstract

Background: This study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model.

Methodology: MSCs harvested from beagles' bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×10(6) labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks.

Principal findings: Home-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining.

Conclusion: It is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal*
  • Dogs
  • Magnetic Resonance Imaging / methods*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Microscopy, Electron, Transmission
  • Stroke / pathology*
  • Stroke / surgery

Grants and funding

This study was supported by National Natural Science Foundation of China (30870710 to Hai-bin Shi, 81000653 to Sheng Liu) and foundation of Research and Innovation Program for postgraduates in Jiangsu Province (CXZZ11.0718 to Shan-shan Lu). http://www.nsfc.gov.cn/Portal0/default152.htm; http://www.ec.js.edu.cn/art/2011/6/11/art_4266_26988.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.