Molecular imaging of bone marrow mononuclear cell survival and homing in murine peripheral artery disease

Koen E.A. Van Der Bogt, Alwine A. Hellingman, Maarten A. Lijkwan, Ernst Jan Bos, Margreet R. De Vries, Juliaan R.M. Van Rappard, Michael P. Fischbein, Paul H. Quax, Robert C. Robbins, Jaap F. Hamming, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

This study aims to provide insight into cellular kinetics using molecular imaging after different transplantation methods of bone marrowderived mononuclear cells (MNCs) in a mouse model of peripheral artery disease (PAD). MNC therapy is a promising treatment for PAD. Although clinical translation has already been established, there is a lack of knowledge about cell behavior after transplantation and about the mechanism whereby MNC therapy might ameliorate complaints of PAD. MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n = 50) underwent femoral artery ligation and were randomized into 4 groups receiving the following: 1) single intramuscular (IM) injection of 2 × 10 6 MNCs; 2) 4 weekly IM injections of 5 × 10 5 MNCs; 3) 2 × 10 6 MNCs intravenously; and 4) phosphate-buffered saline as control. Cells were characterized by flow cytometry and in vitro bioluminescence imaging (BLI). Cell survival, proliferation, and migration were monitored by in vivo BLI, which was validated by ex vivo BLI, post-mortem immunohistochemistry, and flow cytometry. Paw perfusion and neovascularization was measured with laser Doppler perfusion imaging (LDPI) and histology, respectively. In vivo BLI revealed near-complete donor cell death 4 weeks after IM transplantation. After intravenous transplantation, BLI revealed that cells migrated to the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularization were observed, as monitored by LDPI and histology. This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short-lived, MNCs do not preferentially home to injured areas, and MNCs do not significantly stimulate perfusion in this particular model.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalJACC: Cardiovascular Imaging
Volume5
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • cardiovascular disease
  • cell therapy
  • molecular imaging
  • peripheral artery disease

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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