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

Abstract：

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 × 10(6) 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.

journal_name

Cytotherapy

journal_title

Cytotherapy

authors

Richardson JD,Psaltis PJ,Frost L,Paton S,Carbone A,Bertaso AG,Nelson AJ,Wong DT,Worthley MI,Gronthos S,Zannettino AC,Worthley SG

doi

10.1016/j.jcyt.2013.07.016

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

460-70

issue

4

eissn

1465-3249

issn

1477-2566

pii

S1465-3249(13)00645-2

journal_volume

16

pub_type

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