Advancement in Stem Cell Therapy for Ischemic Myocardial Cell: A systematic Review

  • Syeda Beenish Bareeqa Jinnah Medical and Dental College, Karachi, Pakistan
  • Fazeela Bibi Jinnah Medical and Dental College, Karachi, Pakistan
  • Syed Ijlal Ahmed Medical Graduate, Liaquat National Medical College and Hospital, Karachi, Pakistan
  • Syeda Sana Samar Jinnah Sindh Medical University, Karachi, Pakistan
Keywords: Mesenchymal stem cells (MSCs), Myocardial infarction (MI), Cardiomyocytes, Hematopoietic stem cells (HSCs)


Background: Cardiac muscle possesses a limited capacity to regenerate its tissue on its own. It is less likely to reverse the altered cardiac functioning to its normal physiological state after a major myocardial infarction. Stem cell transplantation provided a unique therapeutic approach in managing such injuries. There has been a substantial debate about the complexity, scope and medical application of stem cell transplantation in past few years. Materials and Methods: An extensive review of medical literature was conducted to establish the consensus about the possible mechanism of cell renewal, associated complications and risks of failure of this technique. Twenty cases of mammalian animals and twenty-four cases of stem cell transplantation in human subjects were reviewed. Results: Most common associated complication was re-stenosis of coronary artery. Few clinical trials reported the failure in improving cardiac functioning. The success rate of stem cell transplantation was remarkable in the literature related to experimental animal subjects. Conclusion: It was concluded that renewal of the cardiac cell is a result of induction of angiogenesis and prolonged cell survival. This topic still requires an immense amount of research to fill the gap in adequate knowledge.


Cambria E, Pasqualini FS, Wolint P, Günter J, Steiger J, Bopp A, et al. Translational cardiac stem cell therapy: advancing from first-generation to next-generation cell types. npj Regenerative Medicine. 2017;2(1):17.

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. science. 1999;284(5411):143-7.

Ortic D, Kajstura J, Chimenti S, Jakoniuk I. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410(6829):701.

Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, et al. Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. American Journal of Physiology-Heart and circulatory physiology. 2004;287(6):H2670-H6.

Freyman T, Polin G, Osman H, Crary J, Lu M, Cheng L, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. European heart journal. 2006;27(9):1114-22.

Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE. Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. Journal of molecular and cellular cardiology. 2001;33(5):907-21.

Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93-8.

Tomita S, Li R-K, Weisel RD, Mickle DAG, Kim E-J, Sakai T, et al. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation. 1999;100(suppl 2):II-247-Ii-56.

Nagaya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y, et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 2005;112(8):1128-35.

Sakakibara Y, Tambara K, Lu F, Nishina T, Nagaya N, Nishimura K, et al. Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction. The Annals of thoracic surgery. 2002;74(1):25-30.

Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang J-A, et al. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. The Journal of thoracic and cardiovascular surgery. 2008;135(4):799-808.

Wollert KC, Meyer GP, Lotz J, Lichtenberg SR, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. The Lancet. 2004;364(9429):141-8.

Haider HK, Jiang S, Idris NM, Ashraf M. IGF-1–overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circulation Research. 2008;103(11):1300-8.

Jane-wit D, Altuntas CZ, Johnson JM, Yong S, Wickley PJ, Clark P, et al. β 1-adrenergic receptor autoantibodies mediate dilated cardiomyopathy by agonistically inducing cardiomyocyte apoptosis. Circulation. 2007;116(4):399-410.

Zhang D, Fan G-C, Zhou X, Zhao T, Pasha Z, Xu M, et al. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. Journal of molecular and cellular cardiology. 2008;44(2):281-92.

Hu X, Dai S, Wu W-J, Tan W, Zhu X, Mu J, et al. Stromal cell–derived factor-1α confers protection against myocardial ischemia/reperfusion injury. Circulation. 2007;116(6):654-63.

Zagzag D, Lukyanov Y, Li L, Ali MA, Esencay M, Mendez O, et al. Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Laboratory investigation. 2006;86(12):1221.

Phillips RJ, Mestas J, Gharaee-Kermani M, Burdick MD, Sica A, Belperio JA, et al. Epidermal growth factor and hypoxia-induced expression of CXC chemokine receptor 4 on non-small cell lung cancer cells is regulated by the phosphatidylinositol 3-kinase/PTEN/AKT/mammalian target of rapamycin signaling pathway and activation of hypoxia inducible factor-1α. Journal of Biological Chemistry. 2005;280(23):22473-81.

Burchfield JS, Iwasaki M, Koyanagi M, Urbich C, Rosenthal N, Zeiher AM, et al. Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction. Circulation Research. 2008;103(2):203-11.

White B-MISA. Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466-72.

Penn MS. Importance of the SDF-1: CXCR4 axis in myocardial repair. Am Heart Assoc; 2009.

Khan M, Nickoloff E, Abramova T, Johnson J, Verma SK, Krishnamurthy P, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circulation Research. 2015:CIRCRESAHA. 115.305990.

Stamm C, Westphal B, Kleine H-D, Petzsch M, Kittner C, Klinge H, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. The Lancet. 2003;361(9351):45-6.

Patel AN, Geffner L, Vina RF, Saslavsky J, Urschel HC, Kormos R, et al. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. The Journal of thoracic and cardiovascular surgery. 2005;130(6):1631-8. e2.

Kang H-J, Kim H-S, Zhang S-Y, Park K-W, Cho H-J, Koo B-K, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. The Lancet. 2004;363(9411):751-6.

Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. The Lancet. 2004;363(9411):783-4.

Mao J, Lv Z, Zhuang Y. MicroRNA-23a is involved in tumor necrosis factor-α induced apoptosis in mesenchymal stem cells and myocardial infarction. Experimental and molecular pathology. 2014;97(1):23-30.

Luo L, Tang J, Nishi K, Yan C, Dinh P-U, Cores J, et al. Fabrication of synthetic mesenchymal stem cells for the treatment of acute myocardial infarction in micenovelty and significance. Circulation Research. 2017;120(11):1768-75.

Reinecke H, Murry CE. Cell grafting for cardiac repair. Cardiac Cell and Gene Transfer: Principles, Protocols, and Applications. 2003:97-112.

Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, et al. Haemotopoietic stem cells do not transdifferentiate cardiac myocytes in ischaemic myocardium. Nature. 2004;428:664-8.

Dai W, Hale SL, Martin BJ, Kuang J-Q, Dow JS, Wold LE, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium. Circulation. 2005;112(2):214-23.

Silva GV, Litovsky S, Assad JAR, Sousa ALS, Martin BJ, Vela D, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005;111(2):150-6.

Bel A, Messas E, Agbulut O, Richard P, Samuel J-L, Bruneval P, et al. Transplantation of autologous fresh bone marrow into infarcted myocardium: a word of caution. Circulation. 2003;108(10 suppl 1):II-247-II-52.

Davani S, Marandin A, Mersin N, Royer B, Kantelip B, Hervé P, et al. Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation. 2003;108(10 suppl 1):II-253-II-8.

Ghostine Sd, Carrion C, Souza LCsG, Richard P, Bruneval P, Vilquin J-T, et al. Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation. 2002;106(12 suppl 1):I-131-I-6.

Jian-an W, You-qi F, Chang-ling L, Hong H, Yong S, Bin-jian LV. Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University-Science B. 2005;6(4):242-8.

Brasselet C, Morichetti MC, Messas E, Carrion C, Bissery A, Bruneval P, et al. Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium. European heart journal. 2005;26(15):1551-6.

de Silva R, Raval AN, Hadi M, Gildea KM, Bonifacino AC, Yu Z-X, et al. Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction. European heart journal. 2008;29(14):1772-82.

Doyle B, Sorajja P, Hynes B, Kumar AHS, Araoz PA, Stalboerger PG, et al. Progenitor cell therapy in a porcine acute myocardial infarction model induces cardiac hypertrophy, mediated by paracrine secretion of cardiotrophic factors including TGFβ1. Stem cells and development. 2008;17(5):941-52.

Memon IA, Sawa Y, Miyagawa S, Taketani S, Matsuda H. Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy. The Journal of thoracic and cardiovascular surgery. 2005;130(3):646-53.

Moelker AD, Baks T, Van den Bos EJ, van Geuns RJ, De Feyter PJ, Duncker DJ, et al. Reduction in infarct size, but no functional improvement after bone marrow cell administration in a porcine model of reperfused myocardial infarction. European heart journal. 2006;27(24):3057-64.

Tang J, Xie Q, Pan G, Wang J, Wang M. Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. European journal of cardio-thoracic surgery. 2006;30(2):353-61.

Berry MF, Engler AJ, Woo YJ, Pirolli TJ, Bish LT, Jayasankar V, et al. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. American Journal of Physiology-Heart and circulatory physiology. 2006;290(6):H2196-H203.

Min J-Y, Sullivan MF, Yang Y, Zhang J-P, Converso KL, Morgan JP, et al. Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. The Annals of thoracic surgery. 2002;74(5):1568-75.

Yang Y, Min J-Y, Rana JS, Ke Q, Cai J, Chen Y, et al. VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells. Journal of applied physiology. 2002;93(3):1140-51.

Fujii T, Nagaya N, Iwase T, Murakami S, Miyahara Y, Nishigami K, et al. Adrenomedullin enhances therapeutic potency of bone marrow transplantation for myocardial infarction in rats. American Journal of Physiology-Heart and circulatory physiology. 2005;288(3):H1444-H50.

Strauer BE, Brehm M, Zeus T, Gattermann N, Hernandez A, Sorg RV, et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Deutsche medizinische Wochenschrift (1946). 2001;126(34-35):932-8.

How to Cite
Bareeqa SB, Bibi F, Ahmed SI, Samar SS. Advancement in Stem Cell Therapy for Ischemic Myocardial Cell: A systematic Review. ijhoscr. 12(4):281-9.
Review Article(s)