Results from Functional and Cellular Studies using an Ovine Model to Assess Response to Mesenchymal Stem Cell Therapy after Induction of Myocardial Infarction

  • Ms Elizabeth Bailey, Department Nuclear Medicine, Royal North Shore Hospital, Sydney and University of Sydney, School of MRS, Australia
  • A/Prof Dale Bailey, Department Nuclear Medicine, Royal North Shore Hospital, Sydney and University of Sydney, School of MRS, Australia
  • A/Prof George Bautovich, Department Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia
  • Dr Stephen Hunyor, Cardiac Technoogy Centre/Kolling Institute, Royal North Shore Hospital, Sydney, Australia
  • A/Prof Paul Roach, Department Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia

    • Background: Assessing functional and cellular consequences following myocardial infarction (MI) using large animals has advantages of similarity in size, shape and coronary supply to human heart.

    Aim: To confirm presence of MI and detect recovery of perfusion and function following implantation of ovine bone-marrow derived mesenchymal stem cells (MSC) using intra-myocardial (IM) and intra-coronary (IC) methods.

    Methods: Eighteen ewes (wt: 45-50kg, LV-EDV: 80-90mL) included, with 10 completing protocol (3=control, 4=IM, 3=IC). MIBI MPI SPECT/CT performed at baseline, 5-7 days post induction of MI and 6 weeks post cellular therapy with male MSCs. At completion, sheep sacrificed and heart slices reviewed microscopically to confirm MI, assess neovascularisation and correlate with MPI findings. MPI studies reconstructed using OSEM CT-based AC and analysed using QPS/QGS software. Calculation of Recovery Difference (RD%), Recovery Ratio (RR) and relative change to baseline determined for each study and per segment per study.

    Results: MI confirmed in 10 of 12 studies (1 showed no perfusion abnormality, another pre-existing defect), confirmed anatomically by identification of fibrous scar tissue with lymphoid aggregates, histiocytes and calcium deposits. Reduction in perfusion was 14% to 48%. No improvement in perfusion seen in control (RR=0.8, RD=-16.9) and IC (RR=0.9, RD=-7.1) studies. Significant reperfusion seen on IM studies, with RR=1.5, RD=1.1 and perfusion recovery 8%, around periphery of infarct zone.

    Conclusions: Presence of acute MI identified on MIBI MPI SPECT/CT correlates with anatomical findings. Improvement in perfusion and function at infarct zone seen using IM method of MSC implantation, correlating with significant neovascularisation identified microscopically.