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Circ Res. 2014 Apr 11;114(8):1292-301. doi: 10.1161/CIRCRESAHA.114.302854. Epub 2014 Jan 21.

Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.

Author information

1
From The Interdisciplinary Stem Cell Institute (V.Y.S., J.P.Z., V.K., N.M., D.L.D.V., K.S., I.H.S., S.N.T., A.R.W., C.S., J.D.S., I.K.M., J.M.H., A.W.H.), Departments of Medicine (J.P.Z., K.H.N., I.H.S., M.M., B.T., M.T., J.M.H., A.W.H.), and Radiology (E.G., J.E.F.), University of Miami Miller School of Medicine, FL; Cardiovascular Division, The Johns Hopkins University School of Medicine, Baltimore, MD (G.G., E.B., P.V.J., J.B., A.C.L., R.T.G.); Division of Cell Therapy, EMMES Corporation, Rockville, MD (A.M.M.); and Biocardia Inc, San Carlos, CA (P.A.). I.K.M is currently affiliated with the Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX. J.P.Z. is currently affiliated with Jackson South Community Hospital, Miami, FL. M.T. is currently affiliated with Rush University Medical Center, Chicago, IL.

Abstract

RATIONALE:

Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown.

OBJECTIVE:

To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments.

METHODS AND RESULTS:

Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7 ± 4.4%; n=95; P<0.01) and noninjected segments (-25.1 ± 7.8%; n=148; P<0.001; between-group comparison P<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9 ± 3.3-26.3 ± 3.5%; P=0.003) but not in noninjected scar segments (21.3 ± 2.6-23.5 ± 3.2%; P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20% (12.1 ± 1.2-19.9 ± 2.7%; n=18; P=0.003), versus <20% (31.7 ± 3.4-35.5 ± 3.3%; n=12; P=0.33, between-group comparison P<0.0001).

CONCLUSIONS:

These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

KEYWORDS:

cells; magnetic resonance imaging; myocardial infarction; tomography

PMID:
24449819
PMCID:
PMC4067050
DOI:
10.1161/CIRCRESAHA.114.302854
[Indexed for MEDLINE]
Free PMC Article
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