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Article: Lack of Cardiac Nerve Sprouting after Intramyocardial Transplantation of Bone Marrow-Derived Stem Cells in a Swine Model of Chronic Ischemic Myocardium
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TitleLack of Cardiac Nerve Sprouting after Intramyocardial Transplantation of Bone Marrow-Derived Stem Cells in a Swine Model of Chronic Ischemic Myocardium
 
AuthorsLiu, Y1
Lai, WH1
Liao, SY1
Siu, CW1
Yang, YZ2
Tse, HF1
 
KeywordsArrhythmia
Bone marrow cells
Connecxin 43
Ischemia
Nerve sprouting
 
Issue Date2012
 
PublisherSpringer New York
 
CitationJournal Of Cardiovascular Translational Research, 2012, v. 5 n. 3, p. 359-365 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s12265-012-9350-2
 
AbstractPrevious experimental studies suggested that mesenchymal stem cell transplantation causes cardiac nerve sprouting; however, whether bone marrow (BM)-derived mononuclear cells (MNC) and endothelial progenitor cells (EPC) can also lead to cardiac nerve sprouting and alter gap junction expression remains unclear. We investigated the effect of electroanatomical mapping-guided direct intramyocardial transplantation of BM-MNC (n = 8) and CD31 +EPC (n = 8) compared with saline control (n = 8) on cardiac nerve sprouting and gap junction expression in a swine model of chronic ischemic myocardium. At 12 weeks after transplantation, the distribution and density of cardiac nerve sprouting were determined by staining of tyrosine hydroxylase (TH) and growth associated protein 43(GAP-43) and expression of connexin 43 in the targeted ischemic and remote normal myocardium. After 12 weeks, no animal developed sudden death after the transplantation. There were no significant differences in the number of cells with positive staining of TH and GAP-43 in the ischemic and normal myocardium between three groups. Furthermore, expression of connexin 43 was also similar in the ischemic and normal myocardia in each group of animals (P > 0.05). The results of this study demonstrated that intramyocardial BM-derived MNC or EPC transplantation in a large animal model of chronic myocardial ischemia was not associated with increased cardiac nerve sprouting over the ischemic myocardium. © 2012 The Author(s).
 
ISSN1937-5387
2012 Impact Factor: 3.062
2012 SCImago Journal Rankings: 0.936
 
DOIhttp://dx.doi.org/10.1007/s12265-012-9350-2
 
PubMed Central IDPMC3349852
 
ISI Accession Number IDWOS:000304111300015
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7594/05 M
HKU 7769/08 M
HKU 8/CRF/09
Funding Information:

This study was supported by Research Grants Council of Hong Kong, General Research Fund (No. HKU 7594/05 M, HKU 7769/08 M), Outstanding Researcher Award 2007-2008 (H.F.T) and Collaborative Research Fund of Hong Kong Research Grant Council (HKU 8/CRF/09).

 
ReferencesSiu, C. W., Liao, S. Y., Liu, Y., Lian, Q., & Tse, H. F. (2010). Stem cells for myocardial repair. Thrombosis and Haemostasis, 104(1), 6–12.. doi: 10.1160/TH09-05-0336

Fuchs, S., Kornowski, R., Weisz, G., et al. (2006). Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease. The American Journal of Cardiology, 97(6), 823–829.. doi: 10.1016/j.amjcard.2005.09.132

Gavira, J. J., Nasarre, E., Abizanda, G., et al. (2010). Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. European Heart Journal, 31(8), 1013–1021.. doi: 10.1093/eurheartj/ehp342

Tse, H. F., Siu, C. W., Zhu, S. G., et al. (2007). Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium. European Journal of Heart Failure, 9(8), 747–753.. doi: 10.1016/j.ejheart.2007.03.008

Tse, H. F., Thambar, S., Kwong, Y. L., et al. (2007). Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). European Heart Journal, 28(24), 2998–3005.. doi: 10.1093/eurheartj/ehm485

Van Ramshorst, J., Bax, J. J., Beeres, S. L., et al. (2009). Intramyocardial bone marrow cell injection for chronic myocardial ischemia: A randomized controlled trial. Journal of the American Medical Association, 301(19), 1997–2004.. doi: 10.1001/jama.2009.685

Losordo, D. W., Henry, T. D., Davidson, C., et al. (2011). Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research, 109(4), 428–436.. doi: 10.1161/CIRCRESAHA.111.245993

Liao, S. Y., Liu, Y., Siu, C. W., et al. (2010). Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium. Heart Rhythm, 7(12), 1852–1859.. doi: 10.1016/j.hrthm.2010.09.006

Gepstein, L., Ding, C., Rehemedula, D., et al. (2010). In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies. Stem Cells, 28(12), 2151–2161.. doi: 10.1002/stem.545

Cao, J. M., Chen, L. S., Kenknight, B. H., et al. (2000). Nerve sprouting and sudden cardiac death. Circulation Research, 86(7), 816–821.

Lai, A. C., Wallner, K., Cao, J. M., et al. (2000). Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death. Journal of Cardiovascular Electrophysiology, 11(12), 1345–1351.. doi: 10.1046/j.1540-8167.2000.01345.x

Cao, J. M., Fishbein, M. C., Han, J. B., et al. (2000). Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation, 101(16), 1960–1969.

Pak, H. N., Qayyum, M., Kim, D. T., et al. (2003). Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction. Journal of Cardiovascular Electrophysiology, 14(8), 841–848.. doi: 10.1046/j.1540-8167.2003.03124.x

Kim, S. K., Pak, H. N., Park, J. H., et al. (2010). Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart. Cardiology in the Young, 20(3), 308–317.. doi: 10.1017/S1047951110000132

Meiri, K. F., Pfenninger, K. H., & Willard, M. B. (1986). Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp 46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA, 83(10), 3537–3541.. doi: 10.1073/pnas.83.10.3537

Li, W., Knowlton, D., Van Winkle, D. M., & Habecker, B. A. (2004). Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons. American Journal of Physiology - Heart and Circulatory Physiology, 286(6), H2229–H2236.. doi: 10.1152/ajpheart.00768.2003

Kim, S. U., & De Vellis, J. (2009). Stem cell-based cell therapy in neurological diseases: A review. Journal of Neuroscience Research, 87(10), 2183–2200.. doi: 10.1002/jnr.22054

Wen, Z., Zheng, S., Zhou, C., Wang, J., & Wang, T. (2011). Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. Journal of Cellular and Molecular Medicine, 15(5), 1032–1043.. doi: 10.1111/j.1582-4934.2010.01255.x

Decrock, E., Vinken, M., De Vuyst, E., et al. (2009). Connexin-related signaling in cell death: To live or let die? Cell Death and Differentiation, 16(4), 524–536.. doi: 10.1038/cdd.2008.196

Miura, T., Miki, T., & Yano, T. (2010). Role of the gap junction in ischemic preconditioning in the heart. American Journal of Physiology - Heart and Circulatory Physiology, 298(4), H1115–H1125.. doi: 10.1152/ajpheart.00879.2009
 
GrantsPluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases
 
DC FieldValue
dc.contributor.authorLiu, Y
 
dc.contributor.authorLai, WH
 
dc.contributor.authorLiao, SY
 
dc.contributor.authorSiu, CW
 
dc.contributor.authorYang, YZ
 
dc.contributor.authorTse, HF
 
dc.date.accessioned2012-05-28T08:17:13Z
 
dc.date.available2012-05-28T08:17:13Z
 
dc.date.issued2012
 
dc.description.abstractPrevious experimental studies suggested that mesenchymal stem cell transplantation causes cardiac nerve sprouting; however, whether bone marrow (BM)-derived mononuclear cells (MNC) and endothelial progenitor cells (EPC) can also lead to cardiac nerve sprouting and alter gap junction expression remains unclear. We investigated the effect of electroanatomical mapping-guided direct intramyocardial transplantation of BM-MNC (n = 8) and CD31 +EPC (n = 8) compared with saline control (n = 8) on cardiac nerve sprouting and gap junction expression in a swine model of chronic ischemic myocardium. At 12 weeks after transplantation, the distribution and density of cardiac nerve sprouting were determined by staining of tyrosine hydroxylase (TH) and growth associated protein 43(GAP-43) and expression of connexin 43 in the targeted ischemic and remote normal myocardium. After 12 weeks, no animal developed sudden death after the transplantation. There were no significant differences in the number of cells with positive staining of TH and GAP-43 in the ischemic and normal myocardium between three groups. Furthermore, expression of connexin 43 was also similar in the ischemic and normal myocardia in each group of animals (P > 0.05). The results of this study demonstrated that intramyocardial BM-derived MNC or EPC transplantation in a large animal model of chronic myocardial ischemia was not associated with increased cardiac nerve sprouting over the ischemic myocardium. © 2012 The Author(s).
 
dc.description.naturepublished_or_final_version
 
dc.description.otherSpringer Open Choice, 28 May 2012
 
dc.identifier.citationJournal Of Cardiovascular Translational Research, 2012, v. 5 n. 3, p. 359-365 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s12265-012-9350-2
 
dc.identifier.citeulike10330369
 
dc.identifier.doihttp://dx.doi.org/10.1007/s12265-012-9350-2
 
dc.identifier.eissn1937-5395
 
dc.identifier.epage7
 
dc.identifier.hkuros205039
 
dc.identifier.isiWOS:000304111300015
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7594/05 M
HKU 7769/08 M
HKU 8/CRF/09
Funding Information:

This study was supported by Research Grants Council of Hong Kong, General Research Fund (No. HKU 7594/05 M, HKU 7769/08 M), Outstanding Researcher Award 2007-2008 (H.F.T) and Collaborative Research Fund of Hong Kong Research Grant Council (HKU 8/CRF/09).

 
dc.identifier.issn1937-5387
2012 Impact Factor: 3.062
2012 SCImago Journal Rankings: 0.936
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3349852
 
dc.identifier.pmid22302631
 
dc.identifier.scopuseid_2-s2.0-84865842065
 
dc.identifier.spage1
 
dc.identifier.urihttp://hdl.handle.net/10722/147105
 
dc.identifier.volume5
 
dc.languageEng
 
dc.publisherSpringer New York
 
dc.relation.ispartofJournal of Cardiovascular Translational Research
 
dc.relation.projectPluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases
 
dc.relation.referencesSiu, C. W., Liao, S. Y., Liu, Y., Lian, Q., & Tse, H. F. (2010). Stem cells for myocardial repair. Thrombosis and Haemostasis, 104(1), 6–12.. doi: 10.1160/TH09-05-0336
 
dc.relation.referencesFuchs, S., Kornowski, R., Weisz, G., et al. (2006). Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease. The American Journal of Cardiology, 97(6), 823–829.. doi: 10.1016/j.amjcard.2005.09.132
 
dc.relation.referencesGavira, J. J., Nasarre, E., Abizanda, G., et al. (2010). Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. European Heart Journal, 31(8), 1013–1021.. doi: 10.1093/eurheartj/ehp342
 
dc.relation.referencesTse, H. F., Siu, C. W., Zhu, S. G., et al. (2007). Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium. European Journal of Heart Failure, 9(8), 747–753.. doi: 10.1016/j.ejheart.2007.03.008
 
dc.relation.referencesTse, H. F., Thambar, S., Kwong, Y. L., et al. (2007). Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). European Heart Journal, 28(24), 2998–3005.. doi: 10.1093/eurheartj/ehm485
 
dc.relation.referencesVan Ramshorst, J., Bax, J. J., Beeres, S. L., et al. (2009). Intramyocardial bone marrow cell injection for chronic myocardial ischemia: A randomized controlled trial. Journal of the American Medical Association, 301(19), 1997–2004.. doi: 10.1001/jama.2009.685
 
dc.relation.referencesLosordo, D. W., Henry, T. D., Davidson, C., et al. (2011). Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research, 109(4), 428–436.. doi: 10.1161/CIRCRESAHA.111.245993
 
dc.relation.referencesLiao, S. Y., Liu, Y., Siu, C. W., et al. (2010). Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium. Heart Rhythm, 7(12), 1852–1859.. doi: 10.1016/j.hrthm.2010.09.006
 
dc.relation.referencesGepstein, L., Ding, C., Rehemedula, D., et al. (2010). In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies. Stem Cells, 28(12), 2151–2161.. doi: 10.1002/stem.545
 
dc.relation.referencesCao, J. M., Chen, L. S., Kenknight, B. H., et al. (2000). Nerve sprouting and sudden cardiac death. Circulation Research, 86(7), 816–821.
 
dc.relation.referencesLai, A. C., Wallner, K., Cao, J. M., et al. (2000). Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death. Journal of Cardiovascular Electrophysiology, 11(12), 1345–1351.. doi: 10.1046/j.1540-8167.2000.01345.x
 
dc.relation.referencesCao, J. M., Fishbein, M. C., Han, J. B., et al. (2000). Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation, 101(16), 1960–1969.
 
dc.relation.referencesPak, H. N., Qayyum, M., Kim, D. T., et al. (2003). Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction. Journal of Cardiovascular Electrophysiology, 14(8), 841–848.. doi: 10.1046/j.1540-8167.2003.03124.x
 
dc.relation.referencesKim, S. K., Pak, H. N., Park, J. H., et al. (2010). Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart. Cardiology in the Young, 20(3), 308–317.. doi: 10.1017/S1047951110000132
 
dc.relation.referencesMeiri, K. F., Pfenninger, K. H., & Willard, M. B. (1986). Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp 46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA, 83(10), 3537–3541.. doi: 10.1073/pnas.83.10.3537
 
dc.relation.referencesLi, W., Knowlton, D., Van Winkle, D. M., & Habecker, B. A. (2004). Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons. American Journal of Physiology - Heart and Circulatory Physiology, 286(6), H2229–H2236.. doi: 10.1152/ajpheart.00768.2003
 
dc.relation.referencesKim, S. U., & De Vellis, J. (2009). Stem cell-based cell therapy in neurological diseases: A review. Journal of Neuroscience Research, 87(10), 2183–2200.. doi: 10.1002/jnr.22054
 
dc.relation.referencesWen, Z., Zheng, S., Zhou, C., Wang, J., & Wang, T. (2011). Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. Journal of Cellular and Molecular Medicine, 15(5), 1032–1043.. doi: 10.1111/j.1582-4934.2010.01255.x
 
dc.relation.referencesDecrock, E., Vinken, M., De Vuyst, E., et al. (2009). Connexin-related signaling in cell death: To live or let die? Cell Death and Differentiation, 16(4), 524–536.. doi: 10.1038/cdd.2008.196
 
dc.relation.referencesMiura, T., Miki, T., & Yano, T. (2010). Role of the gap junction in ischemic preconditioning in the heart. American Journal of Physiology - Heart and Circulatory Physiology, 298(4), H1115–H1125.. doi: 10.1152/ajpheart.00879.2009
 
dc.rightsThe Author(s)
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subjectArrhythmia
 
dc.subjectBone marrow cells
 
dc.subjectConnecxin 43
 
dc.subjectIschemia
 
dc.subjectNerve sprouting
 
dc.titleLack of Cardiac Nerve Sprouting after Intramyocardial Transplantation of Bone Marrow-Derived Stem Cells in a Swine Model of Chronic Ischemic Myocardium
 
dc.typeArticle
 
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<item><contributor.author>Liu, Y</contributor.author>
<contributor.author>Lai, WH</contributor.author>
<contributor.author>Liao, SY</contributor.author>
<contributor.author>Siu, CW</contributor.author>
<contributor.author>Yang, YZ</contributor.author>
<contributor.author>Tse, HF</contributor.author>
<date.accessioned>2012-05-28T08:17:13Z</date.accessioned>
<date.available>2012-05-28T08:17:13Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>Journal Of Cardiovascular Translational Research, 2012, v. 5 n. 3, p. 359-365</identifier.citation>
<identifier.issn>1937-5387</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/147105</identifier.uri>
<description.abstract>Previous experimental studies suggested that mesenchymal stem cell transplantation causes cardiac nerve sprouting; however, whether bone marrow (BM)-derived mononuclear cells (MNC) and endothelial progenitor cells (EPC) can also lead to cardiac nerve sprouting and alter gap junction expression remains unclear. We investigated the effect of electroanatomical mapping-guided direct intramyocardial transplantation of BM-MNC (n = 8) and CD31 +EPC (n = 8) compared with saline control (n = 8) on cardiac nerve sprouting and gap junction expression in a swine model of chronic ischemic myocardium. At 12&#160;weeks after transplantation, the distribution and density of cardiac nerve sprouting were determined by staining of tyrosine hydroxylase (TH) and growth associated protein 43(GAP-43) and expression of connexin 43 in the targeted ischemic and remote normal myocardium. After 12&#160;weeks, no animal developed sudden death after the transplantation. There were no significant differences in the number of cells with positive staining of TH and GAP-43 in the ischemic and normal myocardium between three groups. Furthermore, expression of connexin 43 was also similar in the ischemic and normal myocardia in each group of animals (P &gt; 0.05). The results of this study demonstrated that intramyocardial BM-derived MNC or EPC transplantation in a large animal model of chronic myocardial ischemia was not associated with increased cardiac nerve sprouting over the ischemic myocardium. &#169; 2012 The Author(s).</description.abstract>
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<subject>Arrhythmia</subject>
<subject>Bone marrow cells</subject>
<subject>Connecxin 43</subject>
<subject>Ischemia</subject>
<subject>Nerve sprouting</subject>
<title>Lack of Cardiac Nerve Sprouting after Intramyocardial Transplantation of Bone Marrow-Derived Stem Cells in a Swine Model of Chronic Ischemic Myocardium</title>
<type>Article</type>
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<relation.references>Siu, C. W., Liao, S. Y., Liu, Y., Lian, Q., &amp; Tse, H. F. (2010). Stem cells for myocardial repair. Thrombosis and Haemostasis, 104(1), 6&#8211;12.</relation.references>
<relation.references>doi: 10.1160/TH09-05-0336</relation.references>
<relation.references>Fuchs, S., Kornowski, R., Weisz, G., et al. (2006). Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease. The American Journal of Cardiology, 97(6), 823&#8211;829.</relation.references>
<relation.references>doi: 10.1016/j.amjcard.2005.09.132</relation.references>
<relation.references>Gavira, J. J., Nasarre, E., Abizanda, G., et al. (2010). Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. European Heart Journal, 31(8), 1013&#8211;1021.</relation.references>
<relation.references>doi: 10.1093/eurheartj/ehp342</relation.references>
<relation.references>Tse, H. F., Siu, C. W., Zhu, S. G., et al. (2007). Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium. European Journal of Heart Failure, 9(8), 747&#8211;753.</relation.references>
<relation.references>doi: 10.1016/j.ejheart.2007.03.008</relation.references>
<relation.references>Tse, H. F., Thambar, S., Kwong, Y. L., et al. (2007). Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). European Heart Journal, 28(24), 2998&#8211;3005.</relation.references>
<relation.references>doi: 10.1093/eurheartj/ehm485</relation.references>
<relation.references>Van Ramshorst, J., Bax, J. J., Beeres, S. L., et al. (2009). Intramyocardial bone marrow cell injection for chronic myocardial ischemia: A randomized controlled trial. Journal of the American Medical Association, 301(19), 1997&#8211;2004.</relation.references>
<relation.references>doi: 10.1001/jama.2009.685</relation.references>
<relation.references>Losordo, D. W., Henry, T. D., Davidson, C., et al. (2011). Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Research, 109(4), 428&#8211;436.</relation.references>
<relation.references>doi: 10.1161/CIRCRESAHA.111.245993</relation.references>
<relation.references>Liao, S. Y., Liu, Y., Siu, C. W., et al. (2010). Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium. Heart Rhythm, 7(12), 1852&#8211;1859.</relation.references>
<relation.references>doi: 10.1016/j.hrthm.2010.09.006</relation.references>
<relation.references>Gepstein, L., Ding, C., Rehemedula, D., et al. (2010). In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies. Stem Cells, 28(12), 2151&#8211;2161.</relation.references>
<relation.references>doi: 10.1002/stem.545</relation.references>
<relation.references>Cao, J. M., Chen, L. S., Kenknight, B. H., et al. (2000). Nerve sprouting and sudden cardiac death. Circulation Research, 86(7), 816&#8211;821.</relation.references>
<relation.references>Lai, A. C., Wallner, K., Cao, J. M., et al. (2000). Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death. Journal of Cardiovascular Electrophysiology, 11(12), 1345&#8211;1351.</relation.references>
<relation.references>doi: 10.1046/j.1540-8167.2000.01345.x</relation.references>
<relation.references>Cao, J. M., Fishbein, M. C., Han, J. B., et al. (2000). Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation, 101(16), 1960&#8211;1969.</relation.references>
<relation.references>Pak, H. N., Qayyum, M., Kim, D. T., et al. (2003). Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction. Journal of Cardiovascular Electrophysiology, 14(8), 841&#8211;848.</relation.references>
<relation.references>doi: 10.1046/j.1540-8167.2003.03124.x</relation.references>
<relation.references>Kim, S. K., Pak, H. N., Park, J. H., et al. (2010). Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart. Cardiology in the Young, 20(3), 308&#8211;317.</relation.references>
<relation.references>doi: 10.1017/S1047951110000132</relation.references>
<relation.references>Meiri, K. F., Pfenninger, K. H., &amp; Willard, M. B. (1986). Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp 46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA, 83(10), 3537&#8211;3541.</relation.references>
<relation.references>doi: 10.1073/pnas.83.10.3537</relation.references>
<relation.references>Li, W., Knowlton, D., Van Winkle, D. M., &amp; Habecker, B. A. (2004). Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons. American Journal of Physiology - Heart and Circulatory Physiology, 286(6), H2229&#8211;H2236.</relation.references>
<relation.references>doi: 10.1152/ajpheart.00768.2003</relation.references>
<relation.references>Kim, S. U., &amp; De Vellis, J. (2009). Stem cell-based cell therapy in neurological diseases: A review. Journal of Neuroscience Research, 87(10), 2183&#8211;2200.</relation.references>
<relation.references>doi: 10.1002/jnr.22054</relation.references>
<relation.references>Wen, Z., Zheng, S., Zhou, C., Wang, J., &amp; Wang, T. (2011). Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. Journal of Cellular and Molecular Medicine, 15(5), 1032&#8211;1043.</relation.references>
<relation.references>doi: 10.1111/j.1582-4934.2010.01255.x</relation.references>
<relation.references>Decrock, E., Vinken, M., De Vuyst, E., et al. (2009). Connexin-related signaling in cell death: To live or let die? Cell Death and Differentiation, 16(4), 524&#8211;536.</relation.references>
<relation.references>doi: 10.1038/cdd.2008.196</relation.references>
<relation.references>Miura, T., Miki, T., &amp; Yano, T. (2010). Role of the gap junction in ischemic preconditioning in the heart. American Journal of Physiology - Heart and Circulatory Physiology, 298(4), H1115&#8211;H1125.</relation.references>
<relation.references>doi: 10.1152/ajpheart.00879.2009</relation.references>
<identifier.volume>5</identifier.volume>
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<identifier.spage>1</identifier.spage>
<identifier.epage>7</identifier.epage>
<identifier.eissn>1937-5395</identifier.eissn>
<identifier.isi>WOS:000304111300015</identifier.isi>
<description.other>Springer Open Choice, 28 May 2012</description.other>
<relation.project>Pluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases</relation.project>
<identifier.citeulike>10330369</identifier.citeulike>
<bitstream.url>http://hub.hku.hk/bitstream/10722/147105/1/fulltext.pdf</bitstream.url>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Dalian Medical University