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Erschienen in: Surgery Today 2/2018

18.08.2017 | Original Article

Myocardial regenerative therapy using a scaffold-free skeletal-muscle-derived cell sheet in patients with dilated cardiomyopathy even under a left ventricular assist device: a safety and feasibility study

verfasst von: Yasushi Yoshikawa, Shigeru Miyagawa, Koichi Toda, Atsuhiro Saito, Yasushi Sakata, Yoshiki Sawa

Erschienen in: Surgery Today | Ausgabe 2/2018

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Abstract

Background and purpose

Despite promising experimental results, clinically, intramyocardial myoblast injection failed to reverse remodeling and it induced arrhythmogenicity. In contrast, scaffold-free skeletal muscle-derived cell (SC) sheets attenuated cardiac dysfunction and arrhythmogenicity via paracrine effects. We report the first clinical trial of SC sheet implantation (SCSI) conducted in four patients with dilated cardiomyopathy (DCM) supported by a left ventricular assist device (LVAD).

Methods

SC sheets were made from muscle fibers and multi-layered SC sheets were applied to the left ventricular (LV) anterolateral surface via left thoracotomy.

Results

There were no major cardiac adverse events. Ventricular arrhythmia decreased in all except one patient, in whom global LV function did not improve. The LV volume decreased and LV ejection fraction improved in all except the same patient. Systolic wall thickening, reflecting regional wall motion, improved in the sheet-implanted areas, and vessels in the LV apex increased in all patients, suggesting angiogenesis. The LVAD was successfully removed in two patients.

Conclusions

SCSI induced reverse remodeling and angiogenesis, and improved LV function, allowing LVAD removal in two patients, although functional recovery failed to improve in the one non-responder, even with angiogenesis. SCSI is a promising regenerative therapy for DCM patients responsive to this strategy, even with LVAD assistance.
Literatur
1.
Zurück zum Zitat Lala A, Joyce E, Groarke JD, Mehra MR. Challenges in long-term mechanical circulatory support and biological replacement of the failing heart. Circ J. 2014;78:288–99.CrossRefPubMed Lala A, Joyce E, Groarke JD, Mehra MR. Challenges in long-term mechanical circulatory support and biological replacement of the failing heart. Circ J. 2014;78:288–99.CrossRefPubMed
2.
Zurück zum Zitat Toyoda Y, Guy TS, Kashem A. Present status and future perspectives of heart transplantation. Circ J. 2013;77:1097–110.CrossRefPubMed Toyoda Y, Guy TS, Kashem A. Present status and future perspectives of heart transplantation. Circ J. 2013;77:1097–110.CrossRefPubMed
3.
Zurück zum Zitat Dib N, Michler RE, Pagani FD, Wright S, Kereiakes DJ, Lengerich R, et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation. 2005;112:1748–55.CrossRefPubMed Dib N, Michler RE, Pagani FD, Wright S, Kereiakes DJ, Lengerich R, et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation. 2005;112:1748–55.CrossRefPubMed
4.
Zurück zum Zitat Dowell JD, Rubart M, Pasumarthi KB, Soonpaa MH, Field LJ. Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res. 2003;58:336–50.CrossRefPubMed Dowell JD, Rubart M, Pasumarthi KB, Soonpaa MH, Field LJ. Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res. 2003;58:336–50.CrossRefPubMed
5.
Zurück zum Zitat Perez-Ilzarbe M, Agbulut O, Pelacho B, Ciorba C, San Jose-Eneriz E, Desnos M, et al. Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium. Eur J Heart Fail. 2008;10:1065–72.CrossRefPubMed Perez-Ilzarbe M, Agbulut O, Pelacho B, Ciorba C, San Jose-Eneriz E, Desnos M, et al. Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium. Eur J Heart Fail. 2008;10:1065–72.CrossRefPubMed
6.
Zurück zum Zitat Hagege AA, Marolleau JP, Vilquin JT, Alheritiere A, Peyrard S, Duboc D, et al. Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation. 2006;114:I108–13.CrossRefPubMed Hagege AA, Marolleau JP, Vilquin JT, Alheritiere A, Peyrard S, Duboc D, et al. Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation. 2006;114:I108–13.CrossRefPubMed
7.
Zurück zum Zitat Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117:1189–200.CrossRefPubMed Menasche P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation. 2008;117:1189–200.CrossRefPubMed
8.
Zurück zum Zitat Hoashi T, Matsumiya G, Miyagawa S, Ichikawa H, Ueno T, Ono M, et al. Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart. J Thorac Cardiovasc Surg. 2009;138:460–7.CrossRefPubMed Hoashi T, Matsumiya G, Miyagawa S, Ichikawa H, Ueno T, Ono M, et al. Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart. J Thorac Cardiovasc Surg. 2009;138:460–7.CrossRefPubMed
9.
Zurück zum Zitat Kondoh H, Sawa Y, Miyagawa S, Sakakida-Kitagawa S, Memon IA, Kawaguchi N, et al. Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters. Cardiovasc Res. 2006;69:466–75.CrossRefPubMed Kondoh H, Sawa Y, Miyagawa S, Sakakida-Kitagawa S, Memon IA, Kawaguchi N, et al. Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters. Cardiovasc Res. 2006;69:466–75.CrossRefPubMed
10.
Zurück zum Zitat Miyagawa S, Saito A, Sakaguchi T, Yoshikawa Y, Yamauchi T, Imanishi Y, et al. Impaired myocardium regeneration with skeletal cell sheets–a preclinical trial for tissue-engineered regeneration therapy. In: Transplantation. 2010/06/18 ed; 2010. pp. 364–372. Miyagawa S, Saito A, Sakaguchi T, Yoshikawa Y, Yamauchi T, Imanishi Y, et al. Impaired myocardium regeneration with skeletal cell sheets–a preclinical trial for tissue-engineered regeneration therapy. In: Transplantation. 2010/06/18 ed; 2010. pp. 364–372.
11.
Zurück zum Zitat Miyagawa S, Roth M, Saito A, Sawa Y, Kostin S. Tissue-engineered cardiac constructs for cardiac repair. Ann Thorac Surg. 2011;91:320–9.CrossRefPubMed Miyagawa S, Roth M, Saito A, Sawa Y, Kostin S. Tissue-engineered cardiac constructs for cardiac repair. Ann Thorac Surg. 2011;91:320–9.CrossRefPubMed
12.
Zurück zum Zitat Sawa Y, Yoshikawa Y, Toda K, Fukushima S, Yamazaki K, Ono M, et al. Safety and efficacy of autologous skeletal myoblast sheets (TCD-51073) for the treatment of severe chronic heart failure due to ischemic heart disease. Circ J. 2015;79:991–9.CrossRefPubMed Sawa Y, Yoshikawa Y, Toda K, Fukushima S, Yamazaki K, Ono M, et al. Safety and efficacy of autologous skeletal myoblast sheets (TCD-51073) for the treatment of severe chronic heart failure due to ischemic heart disease. Circ J. 2015;79:991–9.CrossRefPubMed
13.
Zurück zum Zitat Matsumiya G, Saitoh S, Sakata Y, Sawa Y. Myocardial recovery by mechanical unloading with left ventricular assist system. Circ J. 2009;73:1386–92.CrossRefPubMed Matsumiya G, Saitoh S, Sakata Y, Sawa Y. Myocardial recovery by mechanical unloading with left ventricular assist system. Circ J. 2009;73:1386–92.CrossRefPubMed
14.
Zurück zum Zitat Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, et al. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res. 2002;90:e40.CrossRefPubMed Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, et al. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res. 2002;90:e40.CrossRefPubMed
15.
Zurück zum Zitat Shudo Y, Taniguchi K, Takeda K, Sakaguchi T, Matsue H, Izutani H, et al. Assessment of regional myocardial wall stress before and after surgical correction of functional ischaemic mitral regurgitation using multidetector computed tomography and novel software system. Eur J Cardiothorac Surg. 2010;38:163–70.CrossRefPubMed Shudo Y, Taniguchi K, Takeda K, Sakaguchi T, Matsue H, Izutani H, et al. Assessment of regional myocardial wall stress before and after surgical correction of functional ischaemic mitral regurgitation using multidetector computed tomography and novel software system. Eur J Cardiothorac Surg. 2010;38:163–70.CrossRefPubMed
16.
Zurück zum Zitat Lessick J, Ben-Haim T, Mutlak D, Abadi S, Agmon Y, Ghersin E. Quantitative evaluation of regional left ventricular function by multidetector computed tomography. J Comput Assist Tomogr. 2009;33:204–10.CrossRefPubMed Lessick J, Ben-Haim T, Mutlak D, Abadi S, Agmon Y, Ghersin E. Quantitative evaluation of regional left ventricular function by multidetector computed tomography. J Comput Assist Tomogr. 2009;33:204–10.CrossRefPubMed
17.
Zurück zum Zitat van den Bos EJ, Thompson RB, Wagner A, Mahrholdt H, Morimoto Y, Thomson LE, et al. Functional assessment of myoblast transplantation for cardiac repair with magnetic resonance imaging. Eur J Heart Fail. 2005;7:435–43.CrossRefPubMed van den Bos EJ, Thompson RB, Wagner A, Mahrholdt H, Morimoto Y, Thomson LE, et al. Functional assessment of myoblast transplantation for cardiac repair with magnetic resonance imaging. Eur J Heart Fail. 2005;7:435–43.CrossRefPubMed
18.
Zurück zum Zitat Miyagawa S, Toda K, Nakamura T, Yoshikawa Y, Fukushima S, Saito S, et al. Building a bridge to recovery: the pathophysiology of LVAD-induced reverse modeling in heart failure. Surg Today. 2016;46:149–54.CrossRefPubMed Miyagawa S, Toda K, Nakamura T, Yoshikawa Y, Fukushima S, Saito S, et al. Building a bridge to recovery: the pathophysiology of LVAD-induced reverse modeling in heart failure. Surg Today. 2016;46:149–54.CrossRefPubMed
19.
Zurück zum Zitat de Jonge N, van Wichen DF, Schipper ME, Lahpor JR, Gmelig-Meyling FH, Robles de Medina EO, et al. Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading. An immunohistochemical analysis of the contractile myofilaments. J Am Coll Cardiol. 2002;39:963–9.CrossRefPubMed de Jonge N, van Wichen DF, Schipper ME, Lahpor JR, Gmelig-Meyling FH, Robles de Medina EO, et al. Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading. An immunohistochemical analysis of the contractile myofilaments. J Am Coll Cardiol. 2002;39:963–9.CrossRefPubMed
20.
Zurück zum Zitat Bruckner BA, Stetson SJ, Perez-Verdia A, Youker KA, Radovancevic B, Connelly JH, et al. Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support. J Heart Lung Transplant. 2001;20:457–64.CrossRefPubMed Bruckner BA, Stetson SJ, Perez-Verdia A, Youker KA, Radovancevic B, Connelly JH, et al. Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support. J Heart Lung Transplant. 2001;20:457–64.CrossRefPubMed
21.
Zurück zum Zitat Zafeiridis A, Jeevanandam V, Houser SR, Margulies KB. Regression of cellular hypertrophy after left ventricular assist device support. Circulation. 1998;98:656–62.CrossRefPubMed Zafeiridis A, Jeevanandam V, Houser SR, Margulies KB. Regression of cellular hypertrophy after left ventricular assist device support. Circulation. 1998;98:656–62.CrossRefPubMed
22.
Zurück zum Zitat Murtuza B, Suzuki K, Bou-Gharios G, Beauchamp JR, Smolenski RT, Partridge TA, et al. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci USA. 2004;101:4216–21.CrossRefPubMedPubMedCentral Murtuza B, Suzuki K, Bou-Gharios G, Beauchamp JR, Smolenski RT, Partridge TA, et al. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci USA. 2004;101:4216–21.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Liu Y, Rajur K, Tolbert E, Dworkin LD. Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney Int. 2000;58:2028–43.CrossRefPubMed Liu Y, Rajur K, Tolbert E, Dworkin LD. Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney Int. 2000;58:2028–43.CrossRefPubMed
24.
Zurück zum Zitat Miyagawa S, Sawa Y, Taketani S, Kawaguchi N, Nakamura T, Matsuura N, et al. Myocardial regeneration therapy for heart failure: hepatocyte growth factor enhances the effect of cellular cardiomyoplasty. Circulation. 2002;105:2556–61.CrossRefPubMed Miyagawa S, Sawa Y, Taketani S, Kawaguchi N, Nakamura T, Matsuura N, et al. Myocardial regeneration therapy for heart failure: hepatocyte growth factor enhances the effect of cellular cardiomyoplasty. Circulation. 2002;105:2556–61.CrossRefPubMed
25.
Zurück zum Zitat Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease. Gene Ther. 2001;8:181–9.CrossRefPubMed Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease. Gene Ther. 2001;8:181–9.CrossRefPubMed
26.
Zurück zum Zitat Lionetti V, Matteucci M, Ribezzo M, Di Silvestre D, Brambilla F, Agostini S, et al. Regional mapping of myocardial hibernation phenotype in idiopathic end-stage dilated cardiomyopathy. J Cell Mol Med. 2014;18:396–414.CrossRefPubMedPubMedCentral Lionetti V, Matteucci M, Ribezzo M, Di Silvestre D, Brambilla F, Agostini S, et al. Regional mapping of myocardial hibernation phenotype in idiopathic end-stage dilated cardiomyopathy. J Cell Mol Med. 2014;18:396–414.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Fitzpatrick JR 3rd, Frederick JR, McCormick RC, Harris DA, Kim AY, Muenzer JR, et al. Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction. J Thorac Cardiovasc Surg. 2010;140:667–76.CrossRefPubMedPubMedCentral Fitzpatrick JR 3rd, Frederick JR, McCormick RC, Harris DA, Kim AY, Muenzer JR, et al. Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction. J Thorac Cardiovasc Surg. 2010;140:667–76.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Abraham MR, Henrikson CA, Tung L, Chang MG, Aon M, Xue T, et al. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ Res. 2005;97:159–67.CrossRefPubMed Abraham MR, Henrikson CA, Tung L, Chang MG, Aon M, Xue T, et al. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ Res. 2005;97:159–67.CrossRefPubMed
29.
Zurück zum Zitat Fukushima S, Varela-Carver A, Coppen SR, Yamahara K, Felkin LE, Lee J, et al. Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation. 2007;115:2254–61.CrossRefPubMed Fukushima S, Varela-Carver A, Coppen SR, Yamahara K, Felkin LE, Lee J, et al. Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. Circulation. 2007;115:2254–61.CrossRefPubMed
30.
Zurück zum Zitat Peters NS, Coromilas J, Severs NJ, Wit AL. Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation. 1997;95:988–96.CrossRefPubMed Peters NS, Coromilas J, Severs NJ, Wit AL. Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation. 1997;95:988–96.CrossRefPubMed
31.
Zurück zum Zitat Yang Y, Min JY, Rana JS, Ke Q, Cai J, Chen Y, et al. VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells. J Appl Physiol. 2002;93:1140–51.CrossRefPubMed Yang Y, Min JY, Rana JS, Ke Q, Cai J, Chen Y, et al. VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells. J Appl Physiol. 2002;93:1140–51.CrossRefPubMed
Metadaten
Titel
Myocardial regenerative therapy using a scaffold-free skeletal-muscle-derived cell sheet in patients with dilated cardiomyopathy even under a left ventricular assist device: a safety and feasibility study
verfasst von
Yasushi Yoshikawa
Shigeru Miyagawa
Koichi Toda
Atsuhiro Saito
Yasushi Sakata
Yoshiki Sawa
Publikationsdatum
18.08.2017
Verlag
Springer Japan
Erschienen in
Surgery Today / Ausgabe 2/2018
Print ISSN: 0941-1291
Elektronische ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-017-1571-1

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