Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy

Luciano C. Amado, Karl H. Schuleri, Anastasios P. Saliaris, Andrew J. Boyle, Robert Helm, Behzad Oskouei, Marco Centola, Virginia Eneboe, Randell Young, Joao Lima, Albert C. Lardo, Alan W. Heldman, Joshua M. Hare

Research output: Contribution to journalArticle

Abstract

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: 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 μm vs. 12.6 ± 0.2 μm, 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.

Original languageEnglish (US)
Pages (from-to)2116-2124
Number of pages9
JournalJournal of the American College of Cardiology
Volume48
Issue number10
DOIs
StatePublished - Nov 21 2006

Fingerprint

Cell- and Tissue-Based Therapy
Mesenchymal Stromal Cells
Regeneration
Myocardial Infarction
Tomography
Magnetic Resonance Imaging
Cardiac Myocytes
Cicatrix
Myocardium
Swine
Injections

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Amado, L. C., Schuleri, K. H., Saliaris, A. P., Boyle, A. J., Helm, R., Oskouei, B., ... Hare, J. M. (2006). Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy. Journal of the American College of Cardiology, 48(10), 2116-2124. https://doi.org/10.1016/j.jacc.2006.06.073

Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy. / Amado, Luciano C.; Schuleri, Karl H.; Saliaris, Anastasios P.; Boyle, Andrew J.; Helm, Robert; Oskouei, Behzad; Centola, Marco; Eneboe, Virginia; Young, Randell; Lima, Joao; Lardo, Albert C.; Heldman, Alan W.; Hare, Joshua M.

In: Journal of the American College of Cardiology, Vol. 48, No. 10, 21.11.2006, p. 2116-2124.

Research output: Contribution to journalArticle

Amado, LC, Schuleri, KH, Saliaris, AP, Boyle, AJ, Helm, R, Oskouei, B, Centola, M, Eneboe, V, Young, R, Lima, J, Lardo, AC, Heldman, AW & Hare, JM 2006, 'Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy', Journal of the American College of Cardiology, vol. 48, no. 10, pp. 2116-2124. https://doi.org/10.1016/j.jacc.2006.06.073
Amado, Luciano C. ; Schuleri, Karl H. ; Saliaris, Anastasios P. ; Boyle, Andrew J. ; Helm, Robert ; Oskouei, Behzad ; Centola, Marco ; Eneboe, Virginia ; Young, Randell ; Lima, Joao ; Lardo, Albert C. ; Heldman, Alan W. ; Hare, Joshua M. / Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy. In: Journal of the American College of Cardiology. 2006 ; Vol. 48, No. 10. pp. 2116-2124.
@article{47e588383ff94e14aaa14a8acc0eaf83,
title = "Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy",
abstract = "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: 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 μm vs. 12.6 ± 0.2 μm, 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.",
author = "Amado, {Luciano C.} and Schuleri, {Karl H.} and Saliaris, {Anastasios P.} and Boyle, {Andrew J.} and Robert Helm and Behzad Oskouei and Marco Centola and Virginia Eneboe and Randell Young and Joao Lima and Lardo, {Albert C.} and Heldman, {Alan W.} and Hare, {Joshua M.}",
year = "2006",
month = "11",
day = "21",
doi = "10.1016/j.jacc.2006.06.073",
language = "English (US)",
volume = "48",
pages = "2116--2124",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "10",

}

TY - JOUR

T1 - Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy

AU - Amado, Luciano C.

AU - Schuleri, Karl H.

AU - Saliaris, Anastasios P.

AU - Boyle, Andrew J.

AU - Helm, Robert

AU - Oskouei, Behzad

AU - Centola, Marco

AU - Eneboe, Virginia

AU - Young, Randell

AU - Lima, Joao

AU - Lardo, Albert C.

AU - Heldman, Alan W.

AU - Hare, Joshua M.

PY - 2006/11/21

Y1 - 2006/11/21

N2 - 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: 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 μm vs. 12.6 ± 0.2 μm, 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.

AB - 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: 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 μm vs. 12.6 ± 0.2 μm, 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.

UR - http://www.scopus.com/inward/record.url?scp=33750944324&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750944324&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2006.06.073

DO - 10.1016/j.jacc.2006.06.073

M3 - Article

VL - 48

SP - 2116

EP - 2124

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 10

ER -