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.
BACKGROUND
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.


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.
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.
Viky Y
VY
Suncion
Eduard
E
Ghersin
Joel E
JE
Fishman
Juan Pablo
JP
Zambrano
Vasileios
V
Karantalis
Nicole
N
Mandel
Katarina H
KH
Nelson
Gary
G
Gerstenblith
Darcy L
DL
DiFede Velazquez
Elayne
E
Breton
Kranthi
K
Sitammagari
Ivonne H
IH
Schulman
Sabrina N
SN
Taldone
Adam R
AR
Williams
Cristina
C
Sanina
Peter V
PV
Johnston
Jeffrey
J
Brinker
Peter
P
Altman
Muzammil
M
Mushtaq
Barry
B
Trachtenberg
Adam M
AM
Mendizabal
Melissa
M
Tracy
Jose
J
Da Silva
Ian K
IK
McNiece
Alberto C
AC
Lardo
Richard T
RT
George
Joshua M
JM
Hare
Alan W
AW
Heldman
D000368:Aged; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002921:Cicatrix / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D024510:Muscle Development / Q000502:physiology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D013318:Stroke Volume / Q000502:physiology; D036542:Tomography, Spiral Computed; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy
cells; magnetic resonance imaging; myocardial infarction; tomography