Embryonic stem cell-derived cardiac myocytes are not ready for human trials

doi:10.1161/CIRCRESAHA.114.304616

Comment

. 2014 Jul 18;115(3):335-8.

doi: 10.1161/CIRCRESAHA.114.304616. Epub 2014 Jun 16.

Embryonic stem cell-derived cardiac myocytes are not ready for human trials

Mark E Anderson¹, Joshua Goldhaber², Steven R Houser², Michel Puceat², Mark A Sussman²

Affiliations

¹ From the Departments of Internal Medicine and Molecular Physiology & Biophysics, Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City (M.E.A); Cedars-Sinai Heart Institute, Los Angeles, CA (J.G.); Department of Physiology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.R.H.); INSERM UMR 910, Génétique médicale et génomique fonctionnelle, Université Aix Marseille, Team Physiopathology of Cardiac Development, Faculté de Medecine La Timone, Marseille, France (M.P.); and Biology Department, Integrated Regenerative Research Institute, San Diego State University, CA (M.A.S.). heartman4ever@icloud.com.
² From the Departments of Internal Medicine and Molecular Physiology & Biophysics, Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City (M.E.A); Cedars-Sinai Heart Institute, Los Angeles, CA (J.G.); Department of Physiology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.R.H.); INSERM UMR 910, Génétique médicale et génomique fonctionnelle, Université Aix Marseille, Team Physiopathology of Cardiac Development, Faculté de Medecine La Timone, Marseille, France (M.P.); and Biology Department, Integrated Regenerative Research Institute, San Diego State University, CA (M.A.S.).

PMID: 24935962
PMCID: PMC4133694
DOI: 10.1161/CIRCRESAHA.114.304616

Comment

Embryonic stem cell-derived cardiac myocytes are not ready for human trials

Mark E Anderson et al. Circ Res. 2014.

. 2014 Jul 18;115(3):335-8.

doi: 10.1161/CIRCRESAHA.114.304616. Epub 2014 Jun 16.

Authors

Mark E Anderson¹, Joshua Goldhaber², Steven R Houser², Michel Puceat², Mark A Sussman²

Affiliations

¹ From the Departments of Internal Medicine and Molecular Physiology & Biophysics, Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City (M.E.A); Cedars-Sinai Heart Institute, Los Angeles, CA (J.G.); Department of Physiology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.R.H.); INSERM UMR 910, Génétique médicale et génomique fonctionnelle, Université Aix Marseille, Team Physiopathology of Cardiac Development, Faculté de Medecine La Timone, Marseille, France (M.P.); and Biology Department, Integrated Regenerative Research Institute, San Diego State University, CA (M.A.S.). heartman4ever@icloud.com.
² From the Departments of Internal Medicine and Molecular Physiology & Biophysics, Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City (M.E.A); Cedars-Sinai Heart Institute, Los Angeles, CA (J.G.); Department of Physiology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.R.H.); INSERM UMR 910, Génétique médicale et génomique fonctionnelle, Université Aix Marseille, Team Physiopathology of Cardiac Development, Faculté de Medecine La Timone, Marseille, France (M.P.); and Biology Department, Integrated Regenerative Research Institute, San Diego State University, CA (M.A.S.).

PMID: 24935962
PMCID: PMC4133694
DOI: 10.1161/CIRCRESAHA.114.304616

Abstract

Recently a preclinical report assessed the efficacy, safety, and feasibility of using human embryonic stem cells to regenerate infarcted myocardium in a non-human primate model. This commentary evaluates that study by pointing out key weaknesses, offering an alternative perspective, and summarizing major unresolved issues. Our conclusion is that significant challenges remain before human embryonic stem cells are ready for use in clinical trials.

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Comment in

Cardiac anisotropy, regeneration, and rhythm.
Pijnappels DA, Schalij MJ, Atsma DE, de Vries AA. Pijnappels DA, et al. Circ Res. 2014 Aug 1;115(4):e6-7. doi: 10.1161/CIRCRESAHA.115.304644. Circ Res. 2014. PMID: 25081134 No abstract available.
Letter by Murry et al regarding article, "Embryonic stem cell-derived cardiac myocytes are not ready for human trials".
Murry CE, Chong JJ, Laflamme MA. Murry CE, et al. Circ Res. 2014 Oct 24;115(10):e28-9. doi: 10.1161/CIRCRESAHA.114.305042. Circ Res. 2014. PMID: 25342771 Free PMC article. No abstract available.
Response to letter regarding article, "Embryonic stem cell-derived cardiac myocytes are not ready for human trials".
Sussman MA, Puceat M. Sussman MA, et al. Circ Res. 2014 Oct 24;115(10):e30-1. doi: 10.1161/CIRCRESAHA.114.305341. Circ Res. 2014. PMID: 25342772 No abstract available.

Comment on

Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.
Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, Mahoney WM, Van Biber B, Cook SM, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem HP, Laflamme MA, Murry CE. Chong JJ, et al. Nature. 2014 Jun 12;510(7504):273-7. doi: 10.1038/nature13233. Epub 2014 Apr 30. Nature. 2014. PMID: 24776797 Free PMC article.

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References

1. Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, Mahoney WM, Van Biber B, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem HP, Laflamme MA, Murry CE. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014 Apr 30; (e-pub ahead of print) - PMC - PubMed
1. Shafa M, Krawetz R, Zhang Y, Rattner JB, Godollei A, Duff HJ, Rancourt DE. Impact of stirred suspension bioreactor culture on the differentiation of murine embryonic stem cells into cardiomyocytes. BMC Cell Biol. 2011;12:53. - PMC - PubMed
1. Niebruegge S, Nehring A, Bär H, Schroeder M, Zweigerdt R, Lehmann J. Cardiomyocyte production in mass suspension culture: embryonic stem cells as a source for great amounts of functional cardiomyocytes. Tissue Eng Part A. 2008;14:1591–601. - PubMed
1. Lecina M, Ting S, Choo A, Reuveny S, Oh S. Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures. Tissue Eng Part C Methods. 2010;16:1609–19. - PubMed
1. Tallini YN, et al. Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca21 indicator GCaMP2. Proc Natl Acad Sci USA. 2006;103:4753–4758. - PMC - PubMed

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[1] Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, Mahoney WM, Van Biber B, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem HP, Laflamme MA, Murry CE. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014 Apr 30; (e-pub ahead of print) - PMC - PubMed

[2] Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, Mahoney WM, Van Biber B, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem HP, Laflamme MA, Murry CE. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014 Apr 30; (e-pub ahead of print) - PMC - PubMed

[3] Shafa M, Krawetz R, Zhang Y, Rattner JB, Godollei A, Duff HJ, Rancourt DE. Impact of stirred suspension bioreactor culture on the differentiation of murine embryonic stem cells into cardiomyocytes. BMC Cell Biol. 2011;12:53. - PMC - PubMed

[4] Shafa M, Krawetz R, Zhang Y, Rattner JB, Godollei A, Duff HJ, Rancourt DE. Impact of stirred suspension bioreactor culture on the differentiation of murine embryonic stem cells into cardiomyocytes. BMC Cell Biol. 2011;12:53. - PMC - PubMed

[5] Niebruegge S, Nehring A, Bär H, Schroeder M, Zweigerdt R, Lehmann J. Cardiomyocyte production in mass suspension culture: embryonic stem cells as a source for great amounts of functional cardiomyocytes. Tissue Eng Part A. 2008;14:1591–601. - PubMed

[6] Niebruegge S, Nehring A, Bär H, Schroeder M, Zweigerdt R, Lehmann J. Cardiomyocyte production in mass suspension culture: embryonic stem cells as a source for great amounts of functional cardiomyocytes. Tissue Eng Part A. 2008;14:1591–601. - PubMed

[7] Lecina M, Ting S, Choo A, Reuveny S, Oh S. Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures. Tissue Eng Part C Methods. 2010;16:1609–19. - PubMed

[8] Lecina M, Ting S, Choo A, Reuveny S, Oh S. Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures. Tissue Eng Part C Methods. 2010;16:1609–19. - PubMed

[9] Tallini YN, et al. Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca21 indicator GCaMP2. Proc Natl Acad Sci USA. 2006;103:4753–4758. - PMC - PubMed

[10] Tallini YN, et al. Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca21 indicator GCaMP2. Proc Natl Acad Sci USA. 2006;103:4753–4758. - PMC - PubMed

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Embryonic stem cell-derived cardiac myocytes are not ready for human trials

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Embryonic stem cell-derived cardiac myocytes are not ready for human trials

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