Therapeutic angiogenesis promotes efficacy of human umbilical cord matrix stem cell transplantation in cardiac repair

Document Type : Original Article

Authors

1 Department of Anatomy, Medical School, Tehran University of Medical Sciences, Tehran, Iran

2 Faculty of Medicine, Tehran Medical Branch, Islamic Azad University, Iran

3 Department of Anatomy, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

4 Department of Pharmacology, Medical School, Tehran University of Medical Sciences, Tehran, Iran

5 Experimental Medicine Research Center, Tums, Tehran, Iran

Abstract

Objective(s):Although previous studies have confirmed the beneficial effects of human umbilical cord matrix stem cell (hUCM) transplantation post myocardial infarction (MI), but this stem cell resource has no potential to induce angiogenesis. In order to achieve the process of angiogenesis and cardiomyocyte regeneration, two required factors for cardiac repair agents were examined namely; hUCM and VEGF on an infarcted heart. The main objective of this research is to investigate the combinatory effect of dhUCM and VEGF transplantation on an infarcted heart.
Materials and Methods:45 min of ligating the left anterior descending coronary artery, the MI-induced
animals received 50 μl PBS, 5 μg VEGF, 5×106 hUCM cells alone, combined with 5 μg VEGF and 5×106 differentiated hUCM cells alone or combined with 5 μg VEGF through intramyocardial injection. MI group, without hUCM and VEGF served as the control group. Left ventricular function and angiogenesis
were also evaluated.
Results: After eight weeks post MI, there were significant rise in left ventricular ejection farction in dhUCM+VEGF group compared to the other treated and non-treated groups (P<0.05). Fibrosis tissue was markedly lower in the dhUCM+VEGF and hUCM+VEGF groups compared to the other treated and non-treated groups (P<0.05). Despite these benefits, vascular density in dhUCM+VEGF group was not markedly different compared to VEGF and hUCM+VEGF groups. The transplanted hUCM and dhUCM cells survived and migrated to the infarcted area.
Conclusion: Our findings demonstrated that the dhUCM cells transplantation combined with VEGF were more efficient on an infarcted heart.

Keywords

References

1. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG et al. Guidelines for the diagnosis and management of heart failure in adults: a report of the american college of cardiology foundation/american heart association task force on practice guidelines developed in collaboration with the international society for heart and lung transplantation. J Am Coll Cardiol 2009;53:e1–e90.
2. Bakhtiary M, Marzban M, Mehdizadeh M, Joghataei MT, Khoei S, Tondar M, et al. Combination of stem cell mobilized by granulocyte-colony stimulating factor and human umbilical cord matrix stem cell: therapy of traumatic brain injury in rats. Iran J Basic Med Sci 2011; 14:327-339.
3. Seghatoleslam M, Jalali M, Nikravesh MR, Hosseini M, Hamidi D, Fazel A. Therapeutic benefit of intravenous administration of human umbilical cord blood- mononuclear cells following intracerebral hemorrhage in rat. Iran J Basic Med Sci 2012;15:860-872.
4. Wu KH, Mo XM, Han ZC, Zhou B. Stem cell engraftment and survival in the ischemic heart.  Ann Thorac Surg 2011; 92:1917–1925.
5. Ahn A, Frishman WH, Gutwein A, Passeri J, Nelson M. Therapeutic angiogenesis: A new treatment approach for ischemic heart disease-Part II. Cardiol Rev 2008; 16:219–229.
6. Pandya NM, Dhalla NS, Santani DD. Angiogenesis-a new target for future therapy. Vascul Pharmacol 2006; 44:265–74.
7. Beohar N, Rapp J, Pandya S, Losordo DW. Rebuilding the damaged heart the potential of cytokines and growth factors in the treatment of ischemic heart disease. Am Coll Cardiol 2010; 56:1287–1297.
8. Mehdizadeh R, Parizadeh MR, Khooei AR, Mehri S, Hosseinzadeh H. Cardioprotective effect of s     Saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iran J Basic Med Sci 2013; 16:56-63.
9. Tao Z, Chen B, Tan X, Zhao Y, Wang L, Zhu T, et al. Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci U S A 2011; 108:2064–2069.
10. Higuchi T, Anton M, Saraste A, Dumler K, Pelisek J, Nekolla SG, et al. Reporter gene PET for monitoring survival of transplanted endothelial progenitor cells in the rat heart after pretreatment with VEGF and atorvastatin. J Nucl Med 2009; 50:1881–1886.
11. Xie X, Cao F, Sheikh AY, Li Z, Connolly AJ, Pei X, et al. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function. Cloning Stem Cells 2007;9:549–563.
12. Peng C, Yang K, Xiang P, Zhang C, Zou L, Wu X,  et al. Effect of transplantation with autologous bone marrow stem cells on acute myocardial infarction. Int J Cardiol 2013; 162:158–165.
13. Bayes-Genis A, Soler-Botija C, Farré J, Sepúlveda P, Raya A, Roura S, et al. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. J Mol Cell Cardiol 2010; 49:771–780.
14. Moretti A, Bellin M, Jung CB, Thies T-M, Takashima Y, Bernshausen A, et al. Mouse and human induced pluripotent stem cells as a source for multipotent Isl1+ cardiovascular progenitors. FASEB Journal  2010; 24:700–711.
15. Fan C-G, Zhang Q, Zhou J. Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev 2011;7:195–207.
16. Taghizadeh RR, Cetrulo KJ, Cetrulo CL. Wharton’s jelly stem cells: future clinical applications. Placenta 2011; 32:S311–S315.
17. Troyer DL, Weiss ML. Concise Review: Wharton’s jelly‐derived cells are a primitive stromal cell population. Stem Cells 2008; 26:591–599.
18. Latifpour M, Nematollahi-Mahani SN, Deilamy M, Azimzadeh BS, Eftekhar-Vaghefi SH, Nabipour F, et al. Improvement in cardiac function following transplantation of human umbilical cord matrix-derived mesenchymal cells. Cardiology 2011; 120:9-18.
19. Hirata Y, Sata M, Motomura N, Takanashi M, Suematsu Y, Ono M, et al. Human umbilical cord blood cells improve cardiac function after myocardial infarction. Biochem Biophys Res Commun 2005; 327:609–614.
20. Chen Y, Liu W, Li W, Gao C. Autologous bone marrow mesenchymal cell transplantation improves left ventricular function in a rabbit model of dilated cardiomyopathy. Exp Mol Pathol 2010; 88:311–315.
21. Bollini S, Smart N, Riley PR. Resident cardiac progenitor cells: at the heart of regeneration. J Mol Cell Cardiol 2011; 50:296–303.
22. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 2004; 22:1330–1337.
23. Yang ZJ, Ma DC, Wang W, Xu SL, Zhang YQ, Chen B, et al. Experimental study of bone marrow-derived mesenchymal stem cells combined with hepatocyte growth factor transplantation via noninfarct-relative artery in acute myocardial infarction. Gene Ther 2006; 13:1564–1568.
24. Müller-Ehmsen J, Krausgrill B, Burst V, Schenk K, Neisen UC, Fries JWU, et al. Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction. J Mol Cell Cardiol 2006; 41:876–884.
25. Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. Am Soc Clin Invest 2001; 07:1395–1402.
26. Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 2003; 9:1195–1201.
27. Collins SD, Baffour R, Waksman R. Cell therapy in myocardial infarction. Cardiovasc Revasc Med 2007; 8:43–51.
28. McGinn AN, Nam HY, Ou M, Hu N, Straub CM, Yockman JW, et al. Bioreducible polymer-transfected skeletal myoblasts for VEGF delivery to acutely ischemic myocardium. Biomaterials 2011; 32:942–949.
29. Byrne AM, Bouchier Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med 2005; 9:777–794.
30. Li Q, Turdi S, Thomas DP, Zhou T, Ren J. Intra-myocardial delivery of mesenchymal stem cells ameliorates left ventricular and cardiomyocyte contractile dysfunction following myocardial infarction. Toxicology lett 2010; 195:119.
31. Baumgartner I, Rauh G, Pieczek A, Wuensch D, Magner M, Kearney M, et al. Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor. Ann Int Med 2000; 132:880–884.
32. Hariawala MD, Horowitz JR, Esakof D, Sheriff DD, Walter DH, Keyt B, et al. VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts. J Surg Res 1996; 63:77–82.
33. Stewart DJ, Kutryk MJB, Fitchett D, Freeman M, Camack N, Su Y, et al. VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: results of the NORTHERN trial. Mol Ther 2009; 17:1109–1115.
34. Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium: deleterious effects of unregulated expression. Circulation. Am Heart Assoc 2000; 102:898–901.
35. Tsoporis JN, Izhar S, Proteau G, Slaughter G, Parker TG. S100B-RAGE dependent VEGF secretion by cardiac myocytes induces myofibroblast proliferation. J Mol Cell Cardiol 2012; 52:464–473.
36. Bougioukas I, Didilis V, Ypsilantis P, Giatromano-laki A, Sivridis E, Lialiaris T, et al. Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium. Cardiovasc Pathol 2007; 16:63-8.
37. Schwarz ER, Speakman MT, Patterson M, Hale SS, Isner JM, Kedes LH, et al. Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat-angiogenesis and angioma formation. J Am Coll Cardiol 2000; 35:1323–1330.
38. Payne TR, Oshima H, Okada M, Momoi N, Tobita K, Keller BB, et al. A relationship between vascular endothelial growth factor, angiogenesis, and cardiac repair after muscle stem cell transplantation          into ischemic hearts. J Am Coll Cardiol 2007; 50:1677–1684.
 

Files

Share

How to cite

Statistics