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Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI
IJCA-21329; No of Pages 2 International Journal of Cardiology xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI Chao-Jun Yang a,1, Jun Yang b,⁎, Jian Yang b, Zhi-Xing Fan a,b,1 a b
Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000 Hubei Province, China Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000 Hubei Province, China
a r t i c l e
i n f o
Article history: Received 21 September 2015 Accepted 4 October 2015 Available online xxxx Keywords: Cardiac atrial appendage stem cells (CASCs) Myocardial infarction (MI) Aldehyde dehydrogenase (ALDH)
Dear Editor, We have read an interesting research titled “Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: A new tool for cardiac repair after MI” reported by Yanick F et al. [1]. They obtained cardiac atrial appendage stem cells (CASCs) from autologous right atrial appendages with high aldehyde dehydrogenase (ALDH) activity in pig. In this study, intramyocardially injected with CASC after myocardial infarction (MI) developed a preservation of cardiac function, including prevention of left ventricle (LV) volumes dilatation, global LV ejection fraction decreasing and regional wall thickening, and improvement of cell viability and wall motion. All these benefits were owing to successful CASC engraftment and cardiomyogenic differentiation. MI has become an important and epidemic health problem with unacceptable high morbidity and mortality over the last few decades 'in the world [2]. Reconstruction of blood supply therapeutic methods in medicine and surgery is the most effective treatment of MI, but necrotic and apoptotic cardiomyocytes couldn't regenerate to the initial function followed by reperfusion. The emergence of stem cells transplantation therapy lighted the way forward. Stem cell populations derived from bone marrow stem cells, cardiac stem cells (CSCs), embryonic stem cells, endothelial progenitors or induced pluripotent stem cells may help cardiomyocytes differentiation and regeneration to maintain car-
⁎ Corresponding author. E-mail address: [email protected] (J. Yang). 1 Contributed equally to this work.
diac function after MI, theoretically. Whereas, bone marrow stem cells that regarded as the topic research of stem cells therapy last decade did not acquire the ideal large benefits [3,4]. In addition to CSCs, other stem cell populations existed a limitation of cardiomyogenic differentiation. Thus, autologous CSCs transportation should be considered as the most suitable for myocardial reparation after MI. According to surface markers and biological characteristics of cardiac progenitors, CSCs contain c-Kit+ CSCs, Sca-1+ CSCs, Islet1+ CSCs and cardiosphere derived cells (CDCs) [5]. In the SCIPIO trial, c-Kit+ CSCs were extracted from the right atrial appendage harvested and transplanted by intracoronary infusion during surgery, providing an improvement of LV systolic function and a reduction of infarct size in myocardial infarction (MI) patients [6,7]. Furthermore, Bolli et al. suggested that c-Kit+ CSCs were based on the ability of differentiation into all cardiac lineages to improve ventricular function [8]. However, Berlo et al. demonstrated that c-Kit+ CSCs were not the main source of cardiomyocytes regeneration in ischemia cardiac and only minimally contribute to cardiomyogenesis by their paracrine mechanism but their direct role is of myocardial cell replacement [9]. Oh et al. discovered Sca-1+ progenitor in heart with auspicious properties for cardiac reparation, including high levels of telomerase, homing to injured myocardium, and differentiation into myocardial cell [10]. The cardiogenic marker islet-1 was deemed to mark with a second heart field progenitor population and could differentiate to diverse cardiovascular cell lineages, such as cardiomyocytes, smooth muscle, and endothelial cell [11–13]. CADUCEUS trial infused autologous CDCs into intracoronary and founded a remission of cardiomyocytes survival, myocardial cell contractility and ventricular thickness without adverse cardiac events [14]. Another research showed that neonatal-derived CDCs performed a stronger regenerative ability than adult-derived CDCs, which may relay on angiogenic cytokines and an augment prevalence of stem cells [15]. Koninckx et al. first identified an aldehyde dehydrogenase (ALDH)+ stem cell population, named CASCs expressed the marker of islet-1, possess an increased cardiac differentiation capacity compared to CDCs stem cells and differentiated cells express the adult cardiomyocytes function [16]. Moreover, the ALDH+ stem cells were more reliable and reproducible to isolate and expand than c-kit+ CSCs [16]. The use of an ALDH+ stem cell population might refer to the effect of ALDH enzyme that enhanced the survival ability of myocardial cell in ischemic condition [17]. Furthermore, long term amplification of CASCs did not change the activity of ALDH and the ability of cardiomyogenic
http://dx.doi.org/10.1016/j.ijcard.2015.10.039 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: C.-J. Yang, et al., Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI, Int J Cardiol (2015), http://dx.doi.org/10.1016/j.ijcard.2015.10.039
2
Correspondence
differentiation [18]. Thus, CASCs is the most optimum candidate of CSCs to repair cardiomyocytes after MI. Dey et al. isolated a subpopulation of Sca-1+ cells that expressed high ALDH activity, which exhibited significant increase in self-renewal, multipotency, high proliferation, and survival [19]. Quijada et al. illustrated that combined transplantation of cardiac progenitor cells and mesenchymal stem cells (MSCs) improved the efficacy of myocardial repair after infarction [20]. The factor secreted from MSCs, like PDGF-AA, could enhance the recruitment of CASCs towards the site of myocardial injury [21]. We supposed a dual cardiac reparation effect may come true with combination of CSCs cell populations themselves or with other stem cell populations. CASCs transportation therapy is a promising approach for myocardial reparation after MI and remains as a large number of clinical trials to be further investigated. Conflict of interest None. Acknowledgments This work was supported by the National Natural Science Foundation of China (Grant Nos.81170133, 81200088 and 81470387), Hubei Province's Science Technology Support program (Grant No. 2015BKA340) and Hubei Province's Outstanding Medical Academic Leader program (Grant No. 201304), China. References [1] Y. Fanton, B. Robic, J.L. Rummens, A. Daniels, S. Windmolders, L. Willems, et al., Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: a new tool for cardiac repair after MI, Int. J. Cardiol. 201 (2015) 10–19. [2] A.S. Go, D. Mozaffarian, V.L. Roger, E.J. Benjamin, J.D. Berry, M.J. Blaha, et al., Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association, Circulation 129 (2014) 399–410. [3] V. Jeevanantham, M. Butler, A. Saad, A. Abdel-Latif, E.K. Zuba-Surma, B. Dawn, Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis, Circulation 126 (2012) 551–568. [4] R.A. Rose, H. Jiang, X. Wang, et al., Bone marrow-derived mesenchymal stromal cells express cardiac-specific markers, retain the stromal phenotype, and do not become functional cardiomyocytes in vitro, Stem Cells 26 (2008) 2884–2892. [5] O. Bergmann, R.D. Bhardwaj, S. Bernard, S. Zdunek, F. Barnabe-Heider, S. Walsh, et al., Evidence for cardiomyocyte renewal in humans, Science 324 (2009) 98–102.
[6] R. Bolli, A.R. Chugh, D. D'Amario, et al., Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial, Lancet 378 (2011) 1847–1857. [7] A.R. Chugh, G.M. Beache, J.H. Loughran, et al., Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance, Circulation 126 (2012) S54–S64. [8] R. Bolli, X.L. Tang, S.K. Sanganalmath, et al., Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy, Circulation 128 (2013) 122–131. [9] J.H. van Berlo, O. Kanisicak, M. Maillet, et al., c-kit+ cells minimally contribute cardiomyocytes to the heart, Nature 509 (2014) 337–341. [10] H. Oh, S.B. Bradfute, T.D. Gallardo, T. Nakamura, V. Gaussin, Y. Mishina, et al., Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction, Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 12313–12318. [11] A. Moretti, L. Caron, A. Nakano, et al., Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification, Cell 127 (2006) 1151–1165. [12] K.L. Laugwitz, A. Moretti, J. Lam, P. Gruber, Y. Chen, S. Woodard, et al., Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages, Nature 433 (2005) 647–653. [13] L. Bu, X. Jiang, S. Martin-Puig, L. Caron, S. Zhu, Y. Shao, et al., Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages, Nature 460 (2009) 113–117. [14] R.R. Makkar, R.R. Smith, K. Cheng, K. Malliaras, L.E. Thomson, D. Berman, et al., Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial, Lancet 379 (2012) 895–904. [15] D.L. Simpson, R. Mishra, S. Sharma, S.K. Goh, S. Deshmukh, S. Kaushal, A strong regenerative ability of cardiac stem cells derived from neonatal hearts, Circulation 126 (2012) S46–S53. [16] R. Koninckx, A. Daniels, S. Windmolders, U. Mees, R. Macianskiene, K. Mubagwa, et al., The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair, Cardiovasc. Res. 97 (2013) 413–423. [17] S.Y. Li, Q. Li, J.J. Shen, et al., Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene in human cardiacmyocytes: role of MAP kinase signaling, J. Mol. Cell. Cardiol. 40 (2006) 283–294. [18] S. Windmolders, L. Willems, A. Daniels, et al., Clinical-scale in vitro expansion preserves biological characteristics of cardiac atrial appendage stem cells, Cell Prolif. 48 (2) (2015) 175–186. [19] D. Dey, G. Pan, N.R. Varma, S.S. Palaniyandi, Sca-1+ cells from fetal heart with high aldehyde dehydrogenase activity exhibit enhanced gene expression for selfrenewal, proliferation, and survival, Oxidative Med. Cell. Longev. 2015 (2015) 730683. [20] P. Quijada, H.T. Salunga, N. Hariharan, J. Cubillo, F. El-Sayed, M. Moshref, et al., Cardiac stem cell hybrids enhance myocardial repair, Circ. Res. 117 (8) (2015) 695–706. [21] S. Windmolders, A. De Boeck, R. Koninckx, A. Daniels, O. De Wever, M. Bracke, et al., Mesenchymal stem cell secreted platelet derived growth factor exerts a promigratory effect on resident cardiac atrial appendage stem cells, J. Mol. Cell. Cardiol. 66 (2014) 177–188.
Please cite this article as: C.-J. Yang, et al., Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI, Int J Cardiol (2015), http://dx.doi.org/10.1016/j.ijcard.2015.10.039
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI Chao-Jun Yang a,1, Jun Yang b,⁎, Jian Yang b, Zhi-Xing Fan a,b,1 a b
Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000 Hubei Province, China Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000 Hubei Province, China
a r t i c l e
i n f o
Article history: Received 21 September 2015 Accepted 4 October 2015 Available online xxxx Keywords: Cardiac atrial appendage stem cells (CASCs) Myocardial infarction (MI) Aldehyde dehydrogenase (ALDH)
Dear Editor, We have read an interesting research titled “Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: A new tool for cardiac repair after MI” reported by Yanick F et al. [1]. They obtained cardiac atrial appendage stem cells (CASCs) from autologous right atrial appendages with high aldehyde dehydrogenase (ALDH) activity in pig. In this study, intramyocardially injected with CASC after myocardial infarction (MI) developed a preservation of cardiac function, including prevention of left ventricle (LV) volumes dilatation, global LV ejection fraction decreasing and regional wall thickening, and improvement of cell viability and wall motion. All these benefits were owing to successful CASC engraftment and cardiomyogenic differentiation. MI has become an important and epidemic health problem with unacceptable high morbidity and mortality over the last few decades 'in the world [2]. Reconstruction of blood supply therapeutic methods in medicine and surgery is the most effective treatment of MI, but necrotic and apoptotic cardiomyocytes couldn't regenerate to the initial function followed by reperfusion. The emergence of stem cells transplantation therapy lighted the way forward. Stem cell populations derived from bone marrow stem cells, cardiac stem cells (CSCs), embryonic stem cells, endothelial progenitors or induced pluripotent stem cells may help cardiomyocytes differentiation and regeneration to maintain car-
⁎ Corresponding author. E-mail address: [email protected] (J. Yang). 1 Contributed equally to this work.
diac function after MI, theoretically. Whereas, bone marrow stem cells that regarded as the topic research of stem cells therapy last decade did not acquire the ideal large benefits [3,4]. In addition to CSCs, other stem cell populations existed a limitation of cardiomyogenic differentiation. Thus, autologous CSCs transportation should be considered as the most suitable for myocardial reparation after MI. According to surface markers and biological characteristics of cardiac progenitors, CSCs contain c-Kit+ CSCs, Sca-1+ CSCs, Islet1+ CSCs and cardiosphere derived cells (CDCs) [5]. In the SCIPIO trial, c-Kit+ CSCs were extracted from the right atrial appendage harvested and transplanted by intracoronary infusion during surgery, providing an improvement of LV systolic function and a reduction of infarct size in myocardial infarction (MI) patients [6,7]. Furthermore, Bolli et al. suggested that c-Kit+ CSCs were based on the ability of differentiation into all cardiac lineages to improve ventricular function [8]. However, Berlo et al. demonstrated that c-Kit+ CSCs were not the main source of cardiomyocytes regeneration in ischemia cardiac and only minimally contribute to cardiomyogenesis by their paracrine mechanism but their direct role is of myocardial cell replacement [9]. Oh et al. discovered Sca-1+ progenitor in heart with auspicious properties for cardiac reparation, including high levels of telomerase, homing to injured myocardium, and differentiation into myocardial cell [10]. The cardiogenic marker islet-1 was deemed to mark with a second heart field progenitor population and could differentiate to diverse cardiovascular cell lineages, such as cardiomyocytes, smooth muscle, and endothelial cell [11–13]. CADUCEUS trial infused autologous CDCs into intracoronary and founded a remission of cardiomyocytes survival, myocardial cell contractility and ventricular thickness without adverse cardiac events [14]. Another research showed that neonatal-derived CDCs performed a stronger regenerative ability than adult-derived CDCs, which may relay on angiogenic cytokines and an augment prevalence of stem cells [15]. Koninckx et al. first identified an aldehyde dehydrogenase (ALDH)+ stem cell population, named CASCs expressed the marker of islet-1, possess an increased cardiac differentiation capacity compared to CDCs stem cells and differentiated cells express the adult cardiomyocytes function [16]. Moreover, the ALDH+ stem cells were more reliable and reproducible to isolate and expand than c-kit+ CSCs [16]. The use of an ALDH+ stem cell population might refer to the effect of ALDH enzyme that enhanced the survival ability of myocardial cell in ischemic condition [17]. Furthermore, long term amplification of CASCs did not change the activity of ALDH and the ability of cardiomyogenic
http://dx.doi.org/10.1016/j.ijcard.2015.10.039 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: C.-J. Yang, et al., Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI, Int J Cardiol (2015), http://dx.doi.org/10.1016/j.ijcard.2015.10.039
2
Correspondence
differentiation [18]. Thus, CASCs is the most optimum candidate of CSCs to repair cardiomyocytes after MI. Dey et al. isolated a subpopulation of Sca-1+ cells that expressed high ALDH activity, which exhibited significant increase in self-renewal, multipotency, high proliferation, and survival [19]. Quijada et al. illustrated that combined transplantation of cardiac progenitor cells and mesenchymal stem cells (MSCs) improved the efficacy of myocardial repair after infarction [20]. The factor secreted from MSCs, like PDGF-AA, could enhance the recruitment of CASCs towards the site of myocardial injury [21]. We supposed a dual cardiac reparation effect may come true with combination of CSCs cell populations themselves or with other stem cell populations. CASCs transportation therapy is a promising approach for myocardial reparation after MI and remains as a large number of clinical trials to be further investigated. Conflict of interest None. Acknowledgments This work was supported by the National Natural Science Foundation of China (Grant Nos.81170133, 81200088 and 81470387), Hubei Province's Science Technology Support program (Grant No. 2015BKA340) and Hubei Province's Outstanding Medical Academic Leader program (Grant No. 201304), China. References [1] Y. Fanton, B. Robic, J.L. Rummens, A. Daniels, S. Windmolders, L. Willems, et al., Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: a new tool for cardiac repair after MI, Int. J. Cardiol. 201 (2015) 10–19. [2] A.S. Go, D. Mozaffarian, V.L. Roger, E.J. Benjamin, J.D. Berry, M.J. Blaha, et al., Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association, Circulation 129 (2014) 399–410. [3] V. Jeevanantham, M. Butler, A. Saad, A. Abdel-Latif, E.K. Zuba-Surma, B. Dawn, Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis, Circulation 126 (2012) 551–568. [4] R.A. Rose, H. Jiang, X. Wang, et al., Bone marrow-derived mesenchymal stromal cells express cardiac-specific markers, retain the stromal phenotype, and do not become functional cardiomyocytes in vitro, Stem Cells 26 (2008) 2884–2892. [5] O. Bergmann, R.D. Bhardwaj, S. Bernard, S. Zdunek, F. Barnabe-Heider, S. Walsh, et al., Evidence for cardiomyocyte renewal in humans, Science 324 (2009) 98–102.
[6] R. Bolli, A.R. Chugh, D. D'Amario, et al., Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial, Lancet 378 (2011) 1847–1857. [7] A.R. Chugh, G.M. Beache, J.H. Loughran, et al., Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance, Circulation 126 (2012) S54–S64. [8] R. Bolli, X.L. Tang, S.K. Sanganalmath, et al., Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy, Circulation 128 (2013) 122–131. [9] J.H. van Berlo, O. Kanisicak, M. Maillet, et al., c-kit+ cells minimally contribute cardiomyocytes to the heart, Nature 509 (2014) 337–341. [10] H. Oh, S.B. Bradfute, T.D. Gallardo, T. Nakamura, V. Gaussin, Y. Mishina, et al., Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction, Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 12313–12318. [11] A. Moretti, L. Caron, A. Nakano, et al., Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification, Cell 127 (2006) 1151–1165. [12] K.L. Laugwitz, A. Moretti, J. Lam, P. Gruber, Y. Chen, S. Woodard, et al., Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages, Nature 433 (2005) 647–653. [13] L. Bu, X. Jiang, S. Martin-Puig, L. Caron, S. Zhu, Y. Shao, et al., Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages, Nature 460 (2009) 113–117. [14] R.R. Makkar, R.R. Smith, K. Cheng, K. Malliaras, L.E. Thomson, D. Berman, et al., Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial, Lancet 379 (2012) 895–904. [15] D.L. Simpson, R. Mishra, S. Sharma, S.K. Goh, S. Deshmukh, S. Kaushal, A strong regenerative ability of cardiac stem cells derived from neonatal hearts, Circulation 126 (2012) S46–S53. [16] R. Koninckx, A. Daniels, S. Windmolders, U. Mees, R. Macianskiene, K. Mubagwa, et al., The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair, Cardiovasc. Res. 97 (2013) 413–423. [17] S.Y. Li, Q. Li, J.J. Shen, et al., Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene in human cardiacmyocytes: role of MAP kinase signaling, J. Mol. Cell. Cardiol. 40 (2006) 283–294. [18] S. Windmolders, L. Willems, A. Daniels, et al., Clinical-scale in vitro expansion preserves biological characteristics of cardiac atrial appendage stem cells, Cell Prolif. 48 (2) (2015) 175–186. [19] D. Dey, G. Pan, N.R. Varma, S.S. Palaniyandi, Sca-1+ cells from fetal heart with high aldehyde dehydrogenase activity exhibit enhanced gene expression for selfrenewal, proliferation, and survival, Oxidative Med. Cell. Longev. 2015 (2015) 730683. [20] P. Quijada, H.T. Salunga, N. Hariharan, J. Cubillo, F. El-Sayed, M. Moshref, et al., Cardiac stem cell hybrids enhance myocardial repair, Circ. Res. 117 (8) (2015) 695–706. [21] S. Windmolders, A. De Boeck, R. Koninckx, A. Daniels, O. De Wever, M. Bracke, et al., Mesenchymal stem cell secreted platelet derived growth factor exerts a promigratory effect on resident cardiac atrial appendage stem cells, J. Mol. Cell. Cardiol. 66 (2014) 177–188.
Please cite this article as: C.-J. Yang, et al., Cardiac atrial appendage stem cells therapy: a novel and promising approach for myocardial reparation after MI, Int J Cardiol (2015), http://dx.doi.org/10.1016/j.ijcard.2015.10.039