Skip to main content Accessibility help
×
Home
Hostname: page-component-55597f9d44-zdfhw Total loading time: 0.274 Render date: 2022-08-15T04:31:50.122Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

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

Published online by Cambridge University Press:  29 March 2010

Sook Kyoung Kim
Affiliation:
Department of Cardiology, Yonsei University Health System, Seoul, Korea
Hui-Nam Pak*
Affiliation:
Department of Cardiology, Yonsei University Health System, Seoul, Korea
Jae Hyung Park
Affiliation:
Department of Cardiology, Yonsei University Health System, Seoul, Korea
Yong Fu Fang
Affiliation:
Department of Cardiology, Korea University Cardiovascular Center, Seoul, Korea
Gwang Il Kim
Affiliation:
Department of Pathology, College of Medicine, Pochon CHA University, Seoul, Korea
Yong Doo Park
Affiliation:
Department of Biomedical Engineering, Korea University, Seoul, Korea
Chun Hwang
Affiliation:
Utah Valley Medical Center, Provo, UT, United States of America
Young-Hoon Kim
Affiliation:
Department of Cardiology, Korea University Cardiovascular Center, Seoul, Korea
Byung Soo Kim
Affiliation:
Department of Hematology, Korea University, Seoul, Korea
*
Correspondence to: H.-N. Pak, MD, PhD, 250 Seungsanno, Seodaemu, Seoul, Republic of Korea 120-752. Tel: +82 2 –2228 58459; Fax: +82 2 393 2041; E-mail: hnpak@yuhs.ac

Abstract

Background

Although electrical pacing is of great utility in many cardiovascular diseases, its effects on the combined cardiac cell therapy have not been established. We hypothesised that mesenchymal stem cell transplantation changes cardiac sympathetic nerve and gap junction, and concomitant pacing has additional biological effects.

Methods

We monitored cardiac rhythm for 4 weeks after human mesenchymal stem cell transplantation (1 × 107, epicardial injection) in 18 dogs in vivo, seven human mesenchymal stem cell with pacing, six human mesenchymal stem cell, and five sham, and evaluated the sympathetic innervation, nerve growth factor-β; tyrosine hydroxylase, angiogenesis, von Willebrand factor, and connexin43 expressions by real time (RT)–polymerase chain reaction and immunostaining. We also measured mRNA expressions of nerve growth factor-β, von Willebrand factor, and connexin43 in vitro culture of human mesenchymal stem cell with or without pacing.

Results

Human mesenchymal stem cell transplanted hearts expressed higher mRNA of nerve growth factor-β (p < 0.01) with sympathetic nerves (p < 0.05), higher mRNA of von Willebrand factor (p < 0.001) with angiogenesis (p < 0.001), but lower mRNA of connexin43 (p < 0.0001) with reduced gap junctions (p < 0.001) than sham. Pacing with human mesenchymal stem cell transplantation resulted in higher expression of mRNA of connexin43 (p < 0.02) and gap junctions (p < 0.001) compared with sham. In contrast, in vitro paced mesenchymal stem cell reduced expression of connexin43 mRNA (p < 0.02).

Conclusion

Human mesenchymal stem cell transplantation increased cardiac sympathetic innervation and angiogenesis, but reduced gap junction after transplanted in the canine heart. In contrast, concomitant electrical pacing increased gap junction expression by paracrine action.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Weissman, IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 2000; 287: 14421446.CrossRefGoogle ScholarPubMed
2. Assmus, B, Honold, J, Schachinger, V, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355: 12221232.CrossRefGoogle ScholarPubMed
3. Tse, WT, Pendleton, JD, Beyer, WM, Egalka, MC, Guinan, EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75: 389397.CrossRefGoogle ScholarPubMed
4. Le Blanc, K, Tammik, C, Rosendahl, K, Zetterberg, E, Ringden, O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003; 31: 890896.CrossRefGoogle ScholarPubMed
5. Bartholomew, A, Patil, S, Mackay, A, et al. Baboon mesenchymal stem cells can be genetically modified to secrete human erythropoietin in vivo. Hum Gene Ther 2001; 12: 15271541.CrossRefGoogle ScholarPubMed
6. Liechty, KW, MacKenzie, TC, Shaaban, AF, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000; 6: 12821286.Google Scholar
7. Saito, T, Kuang, JQ, Bittira, B, Al-Khaldi, A, Chiu, RC. Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 2002; 74: 1924; discussion 24.CrossRefGoogle ScholarPubMed
8. Abraham, WT, Fisher, WG, Smith, AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002; 346: 18451853.CrossRefGoogle ScholarPubMed
9. Cleland, JG, Daubert, JC, Erdmann, E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005; 352: 15391549.CrossRefGoogle ScholarPubMed
10. Pak, HN, Qayyum, M, Kim, DT, et al. Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a Swine model of myocardial infarction. J Cardiovasc Electrophysiol 2003; 14: 841848.CrossRefGoogle Scholar
11. Cao, JM, Chen, LS, KenKnight, BH, et al. Nerve sprouting and sudden cardiac death. Circ Res 2000; 86: 816821.CrossRefGoogle ScholarPubMed
12. Plotnikov, AN, Shlapakova, I, Szabolcs, MJ, et al. Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 2007; 116: 706713.CrossRefGoogle ScholarPubMed
13. Hamabe, A, Okuyama, Y, Miyauchi, Y, et al. Correlation between anatomy and electrical activation in canine pulmonary veins. Circulation 2003; 107: 15501555.CrossRefGoogle ScholarPubMed
14. Zhou, S, Chen, LS, Miyauchi, Y, et al. Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs. Circ Res 2004; 95: 7683.CrossRefGoogle ScholarPubMed
15. Pittenger, MF, Mackay, AM, Beck, SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143147.CrossRefGoogle ScholarPubMed
16. Menasche, P, Hagege, AA, Vilquin, JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003; 41: 10781083.CrossRefGoogle ScholarPubMed
17. Chang, MG, Tung, L, Sekar, RB, et al. Proarrhythmic potential of mesenchymal stem cell transplantation revealed in an in vitro coculture model. Circulation 2006; 113: 18321841.CrossRefGoogle Scholar
18. Beeres, SL, Atsma, DE, van der Laarse, A, et al. Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures. J Am Coll Cardiol 2005; 46: 19431952.CrossRefGoogle ScholarPubMed
19. Fukushima, S, Varela-Carver, A, Coppen, SR, 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: 22542261.CrossRefGoogle ScholarPubMed
20. Schachinger, V, Erbs, S, Elsasser, A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006; 355: 12101221.CrossRefGoogle ScholarPubMed
21. Lunde, K, Solheim, S, Aakhus, S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 11991209.CrossRefGoogle ScholarPubMed
22. Martins, JB, Zipes, DP. Effects of sympathetic and vagal nerves on recovery properties of the endocardium and epicardium of the canine left ventricle. Circ Res 1980; 46: 100110.CrossRefGoogle ScholarPubMed
23. Opthof, T, Misier, AR, Coronel, R, et al. Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. Circ Res 1991; 68: 12041215.CrossRefGoogle ScholarPubMed
24. Valiunas, V, Doronin, S, Valiuniene, L, et al. Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. J Physiol 2004; 555: 617626.CrossRefGoogle ScholarPubMed
25. Pijnappels, DA, Schalij, MJ, van Tuyn, J, et al. Progressive increase in conduction velocity across human mesenchymal stem cells is mediated by enhanced electrical coupling. Cardiovasc Res 2006; 72: 282291.CrossRefGoogle ScholarPubMed
26. Hahn, JY, Cho, HJ, Kang, HJ, et al. Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J Am Coll Cardiol 2008; 51: 933943.CrossRefGoogle ScholarPubMed
27. Zhuang, J, Yamada, KA, Saffitz, JE, Kleber, AG. Pulsatile stretch remodels cell-to-cell communication in cultured myocytes. Circ Res 2000; 87: 316322.CrossRefGoogle ScholarPubMed
28. Chilton, L, Giles, WR, Smith, GL. Evidence of intercellular coupling between co-cultured adult rabbit ventricular myocytes and myofibroblasts. J Physiol 2007; 583: 225236.CrossRefGoogle ScholarPubMed
29. Kawahara, Y, Yamaoka, K, Iwata, M, et al. Novel electrical stimulation sets the cultured myoblast contractile function to ‘on’. Pathobiology 2006; 73: 288294.CrossRefGoogle Scholar
30. Hudlicka, O, Wright, AJ, Ziada, AM. Angiogenesis in the heart and skeletal muscle. Can J Cardiol 1986; 2: 120123.Google ScholarPubMed
13
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

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
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

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
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

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
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *