CLINICAL RESEARCH · CARDIAC REGENERATION · DREAM BODY CLINIC
Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy
Published in the Journal of the American College of Cardiology, 2006 · Amado et al. · Johns Hopkins University School of Medicine
Study Objectives
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
- MDCT demonstrated increasing thickness of sub-endocardial viable myocardium in MSC-treated animals: 1.0±0.2 mm to 2.0±0.3 mm (p=0.028)
- 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
- Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance
- Regenerated rim was composed of morphologically normal cardiomyocytes — smaller in MSC-treated vs. control subjects (11.6±0.2 μm vs. 12.6±0.2 μm, p=0.05), consistent with regeneration rather than hypertrophy
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.
(J Am Coll Cardiol 2006;48:2116–24) © 2006 by the American College of Cardiology Foundation
Full Study
Access the complete peer-reviewed study published in the Journal of the American College of Cardiology:
Study Citation
Amado LC, Schuleri KH, Saliaris AP, Boyle AJ, Helm R, Oskouei B, Centola M, Eneboe V, Young R, Lima JAC, Lardo AC, Heldman AW, Hare JM. Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy. Journal of the American College of Cardiology. 2006;48(10):2116–2124. Johns Hopkins University School of Medicine, Institute for Cell Engineering.
References
- Pfeffer M, Braunwald E. Ventricular remodeling after MI. Circulation 1990;81:1161–72.
- Orlic D et al. Mobilized bone marrow cells repair the infarcted heart. Proc Natl Acad Sci USA 2001;98:10344–9.
- Orlic D et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–5.
- Britten MB et al. Infarct remodeling after intracoronary progenitor cell treatment. Circulation 2003;108:2212–8.
- Assmus B et al. TOPCARE-AMI. Circulation 2002;106:3009–17.
- Wollert KC et al. BOOST randomised controlled clinical trial. Lancet 2004;364:141–8.
- Mangi AA et al. Mesenchymal stem cells modified with Akt prevent remodeling. Nat Med 2003;9:1195–201.
- Laflamme MA, Murry CE. Regenerating the heart. Nat Biotech 2005;23:845–56.
- Boyle AJ et al. Stem cell therapy for cardiac repair: ready for the next step. Circulation 2006;114:339–52.
- Amado LC et al. Cardiac repair with intramyocardial injection of allogeneic MSCs. Proc Natl Acad Sci USA 2005;102:11474–9.
- Valiunas V et al. Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. J Physiol 2004;555:617–26.
- Berry MF et al. MSC injection after MI improves myocardial compliance. Am J Physiol 2006;290:H2196–2203.
- Gnecchi M et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified MSCs. Nat Med 2005;11:367–8.
- Barbash IM et al. Systemic delivery of bone marrow-derived MSCs to the infarcted myocardium. Circulation 2003;108:863–8.
- Nagaya N et al. Intravenous administration of MSCs improves cardiac function in rats. Am J Physiol 2004;287:H2670–6.