Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction

James D. Richardson, Peter J. Psaltis, Lachlan Frost, Sharon Paton, Angelo Carbone, Angela G. Bertaso, Adam J. Nelson, Dennis T.L. Wong, Matthew I. Worthley, Stan Gronthos, Andrew C.W. Zannettino, Stephen G. Worthley

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20 Citations (Scopus)


Background aims: Traditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs). Methods: Three groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 106 cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI. Results: Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium. Conclusions: Repeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction.

Original languageEnglish
Pages (from-to)460-470
Number of pages11
Issue number4
Publication statusPublished - Apr 2014
Externally publishedYes


  • Cardiac magnetic resonance
  • Hypoxic conditioning
  • Mesenchymal stromal cells
  • Multiple intervention
  • Myocardial infarction
  • Optimization
  • Prospective isolation
  • Repair
  • Timing

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