Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans: Histological analysis of cell survival and differentiation

Francis D. Pagani, Harout DerSimonian, Agatha Zawadzka, Kristie Wetzel, Albert S.B. Edge, Douglas B. Jacoby, Jonathan H. Dinsmore, Susan Wright, Tom H. Aretz, Howard Eisen, Keith D. Aaronson

Research output: Contribution to journalArticle

403 Citations (Scopus)

Abstract

OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.

Original languageEnglish (US)
Pages (from-to)879-888
Number of pages10
JournalJournal of the American College of Cardiology
Volume41
Issue number5
DOIs
StatePublished - Mar 5 2003

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Skeletal Myoblasts
Heart-Assist Devices
Cell Differentiation
Cell Survival
Myocardium
Ischemia
Myoblasts
Transplants
Heart Transplantation
Skeletal Muscle
Skeletal Muscle Myosins
Muscles
Myosin Heavy Chains
Cell Separation
Skeletal Muscle Fibers
Quadriceps Muscle
Cardiomyopathies
Muscle Cells
Heart Diseases
Heart Failure

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Pagani, Francis D. ; DerSimonian, Harout ; Zawadzka, Agatha ; Wetzel, Kristie ; Edge, Albert S.B. ; Jacoby, Douglas B. ; Dinsmore, Jonathan H. ; Wright, Susan ; Aretz, Tom H. ; Eisen, Howard ; Aaronson, Keith D. / Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans : Histological analysis of cell survival and differentiation. In: Journal of the American College of Cardiology. 2003 ; Vol. 41, No. 5. pp. 879-888.
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abstract = "OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.",
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Pagani, FD, DerSimonian, H, Zawadzka, A, Wetzel, K, Edge, ASB, Jacoby, DB, Dinsmore, JH, Wright, S, Aretz, TH, Eisen, H & Aaronson, KD 2003, 'Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans: Histological analysis of cell survival and differentiation', Journal of the American College of Cardiology, vol. 41, no. 5, pp. 879-888. https://doi.org/10.1016/S0735-1097(03)00081-0

Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans : Histological analysis of cell survival and differentiation. / Pagani, Francis D.; DerSimonian, Harout; Zawadzka, Agatha; Wetzel, Kristie; Edge, Albert S.B.; Jacoby, Douglas B.; Dinsmore, Jonathan H.; Wright, Susan; Aretz, Tom H.; Eisen, Howard; Aaronson, Keith D.

In: Journal of the American College of Cardiology, Vol. 41, No. 5, 05.03.2003, p. 879-888.

Research output: Contribution to journalArticle

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T1 - Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans

T2 - Histological analysis of cell survival and differentiation

AU - Pagani, Francis D.

AU - DerSimonian, Harout

AU - Zawadzka, Agatha

AU - Wetzel, Kristie

AU - Edge, Albert S.B.

AU - Jacoby, Douglas B.

AU - Dinsmore, Jonathan H.

AU - Wright, Susan

AU - Aretz, Tom H.

AU - Eisen, Howard

AU - Aaronson, Keith D.

PY - 2003/3/5

Y1 - 2003/3/5

N2 - OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.

AB - OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.

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