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Angiogenesis

, Volume 16, Issue 4, pp 773–784 | Cite as

Human vasculogenic cells form functional blood vessels and mitigate adverse remodeling after ischemia reperfusion injury in rats

  • Kyu-Tae Kang
  • Matthew Coggins
  • Chunyang Xiao
  • Anthony Rosenzweig
  • Joyce BischoffEmail author
Original Paper

Abstract

Cell-based therapies to restore heart function after infarction have been tested in pre-clinical models and clinical trials with mixed results, and will likely require both contractile cells and a vascular network to support them. We and others have shown that human endothelial colony forming cells (ECFC) combined with mesenchymal progenitor cells (MPC) can be used to “bio-engineer” functional human blood vessels. Here we investigated whether ECFC + MPC form functional vessels in ischemic myocardium and whether this affects cardiac function or remodeling. Myocardial ischemia/reperfusion injury (IRI) was induced in 12-week-old immunodeficient rats by ligation of the left anterior descending coronary artery. After 40 min, myocardium was reperfused and ECFC + MPC (2 × 106 cells, 2:3 ratio) or PBS was injected. Luciferase assays after injection of luciferase-labeled ECFC + MPC showed that 1,500 ECFC were present at day 14. Human ECFC-lined perfused vessels were directly visualized by femoral vein injection of a fluorescently-tagged human-specific lectin in hearts injected with ECFC + MPC but not PBS alone. While infarct size at day 1 was no different, LV dimensions and heart weight to tibia length ratios were lower in cell-treated hearts compared with PBS at 4 months, suggesting post-infarction remodeling was ameliorated by local cell injection. Fractional shortening, LV wall motion score, and fibrotic area were not different between groups at 4 months. However, pressure–volume loops demonstrated improved cardiac function and reduced volumes in cell-treated animals. These data suggest that myocardial delivery of ECFC + MPC at reperfusion may provide a therapeutic strategy to mitigate LV remodeling and cardiac dysfunction after IRI.

Keywords

Ischemic myocardium ECFC MPC Angiogenesis Cardiac function 

Notes

Acknowledgments

Supported by HL09262 (JB, TR) and K08-HL098569 (MC). We thank Dr. David Zurokowski, Boston Children’s Hospital, for advice on the statistical analyses. We thank Thomas Neufeld for the excellent technical assistance on fibrosis analysis.

Conflict of interest

The authors have no conflicts of interest to disclose.

Supplementary material

10456_2013_9354_MOESM1_ESM.docx (1 mb)
Supplementary material 1 (DOCX 1,069 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Kyu-Tae Kang
    • 1
    • 2
  • Matthew Coggins
    • 3
  • Chunyang Xiao
    • 3
  • Anthony Rosenzweig
    • 3
  • Joyce Bischoff
    • 1
    Email author
  1. 1.Vascular Biology Program and Department of Surgery, Boston Children’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.College of PharmacyDuksung Women’s UniversitySeoulRepublic of Korea
  3. 3.Cardiovascular Division, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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