Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy.
OBJECTIVE
The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI).


BACKGROUND
Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood.


METHODS
We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone.


RESULTS
Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mum vs. 12.6 +/- 0.2 mum, p < 0.05).


CONCLUSIONS
With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.
Amado
Luciano C
LC
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Schuleri
Karl H
KH
Saliaris
Anastasios P
AP
Boyle
Andrew J
AJ
Helm
Robert
R
Oskouei
Behzad
B
Centola
Marco
M
Eneboe
Virginia
V
Young
Randell
R
Lima
Joao A C
JA
Lardo
Albert C
AC
Heldman
Alan W
AW
Hare
Joshua M
JM
D000818:Animals; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D012038:Regeneration; D013552:Swine; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods