Mononuclear cells promote mesenchymal stem cell migration after myocardial infarction

doi:10.3969/j.issn.2095-4344.2014.01.020

Abstract

Abstract:

BACKGROUND: The mechanisms of mesenchymal stem cells directionally homing to infarcted myocardium post myocardial infarction are still unclear.
OBJECTIVE: To investigate the role of stromal cell derived factor-1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis on mesenchymal stem cell migration promoted by mononuclear cells after myocardial infarction.
METHODS: Cardiomyocytes and mesenchymal stem cells were respectively isolated from suckling and adult Sprague-Dawley rats. Twelve healthy Sprague-Dawley rats were selected (six rats for myocardial infarction models and six for sham models), then circulating mononuclear cells were isolated. 4,6-Diamino-2-phenyl indole-labeled mesenchymal stem cells, cardiomyocytes and mononuclear cells were cultured into the upper, middle and lower layers of the tri-chamber coculture system, respectively. In this experiment, there were four groups: myocardial infarction group, AMD3100 (CXCR4 inhibitor) group, sham group and blank control group. After 48 hours, the number of migrating mesenchymal stem cells with blue-lighting nucleus was calculated under fluoroscope. Immunocytochemistry and immunofluorescent staining was used to detect SDF-1 expression in cardiomyocytes and CXCR4 expression in mesenchymal stem cells, respectively.
RESULTS AND CONCLUSION: Migrating mesenchymal stem cells with positive expression of CXCR4 were observed in each group other than the blank control group. The number of migrating mesenchymal stem cells was higher in the myocardial infarction group than in the other groups. Tumor necrosis factor-α neutralizing antibody and CXCR4 inhibitor AMD3100 could obviously reduce the number of migrating mesenchymal stem cells (P < 0.05). Cardiomyocytes in each group expressed SDF-1 positively. The gray values of SDF-1 expression in the myocardial infarction and AMD3100 groups were significantly higher than those in the sham and blank control groups (P < 0.05). SDF-1/CXCR4 axis plays a certain role in mesenchymal stem cells migration promoted by mononuclear cells after myocardial infarction.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: mesenchymal stem cells, monocytes, receptors, chemokine, myocaridal ischemia, cell movement

CLC Number:

R394.2

Zhang Ying, Liao Li-qiang, Zhang Xiao-gang. Mononuclear cells promote mesenchymal stem cell migration after myocardial infarction[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(1): 119-124.

Figures/Tables 3

References

[1] Li Z, Guo J, Chang Q,et al. Paracrine role for mesenchymal stem cells in acute myocardial infarction. Biol Pharm Bull. 2009;32(8):1343-1346.

[2] Buccini S, Haider KH, Ahmed RP, et al. Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. Basic Res Cardiol. 2012;107(6):301.

[3] Mathieu E, Lamirault G, Toquet C,et al. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction. PLoS One. 2012;7(12):e51991.

[4] Houtgraaf JH, de Jong R, Kazemi K,et al. Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res. 2013;113(2):153-166.

[5] Williams AR, Hatzistergos KE, Addicott B,et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013;127(2):213-223.

[6] Barbash IM, Chouraqui P, Baron J,et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation. 2003;108(7):863-868.

[7] Wang T, Sun S, Wan Z,et al.Effects of bone marrow mesenchymal stem cells in a rat model of myocardial infarction. Resuscitation. 2012;83(11):1391-1396.

[8] Mao Y, Li SN, Mao XB, et al. Therapeutic effect of transplantation of bone marrow mesenchymal stem cells over-expressing Cx43 on heart failure in post-infarction rats. Zhonghua Yi Xue Za Zhi. 2011;91(28):1982-1986.

[9] Fishbein MC, Maclean D, Maroko PR. Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Am J Pathol. 1978;90(1):57-70.

[10] 廖礼强,张晓刚,史若飞,等.心肌梗死大鼠单个核细胞分泌TNF-α对间充质干细胞迁移的影响[J].解放军医学杂志,2010,35(7): 807-810.

[11] 廖礼强,张晓刚,史若飞,等.微血管内皮细胞诱导骨髓间充质干细胞心肌样分化的作用及移植可行性[J].中国组织工程研究与临床康复, 2009,13(40): 7811-7816.

[12] 王佳南,张晓刚,汤为学,等.新生大鼠心肌细胞原代培养方法的改良[J].重庆医科大学学报,2009, 34(5):600-603.

[13] Wollert KC, Drexler H. Mesenchymal stem cells for myocardial infarction: promises and pitfalls. Circulation. 2005; 112(2):151-153.

[14] 于玲范,金丹玲,周晶.细胞间直接接触对骨髓间充质干细胞分化为心肌细胞作用的研究[J].哈尔滨医科大学学报,2006,40(2): 124-127.

[15] 袁岩,陈连凤,张抒扬,等.心肌细胞裂解液对骨髓间充质干细胞向心肌细胞分化诱导作用的研究[J].中华心血管病杂志,2005; 33(2):170-173.

[16] Wang TZ, Ma AQ, Xu ZY, et al. Differentiation of mesenchymal stem cells into cardiomyocytes induced by cardiomyocytes. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2005;30(3):270-275.

[17] Li X, Yu X, Lin Q, et al. Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment.J Mol Cell Cardiol. 2007;42(2):283-284.

[18] Plotnikov EY, Khryapenkova TG, Vasileva AK, et al. Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in coculture. J Cell Mol Med. 2008;50(1): 31-39.

[19] 付小兵,程飚. 成体干细胞研究及其可能的临床应用[J].中华医学杂志,2005,85(27):1878-1880

[20] Roche R, Hoareau L, Mounet F, et al. Adult stem cells for cardiovascular diseases: the adipose tissue potential. Expert Opin Biol Ther. 2007;7(6):791-798.

[21] Shim WS, Jiang S, Wong P, et al. Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells. Biochem Biophys Tes Commun. 2004;324(2):481-488.

[22] Tamaki T, Akatsuka A, Okada Y, et al.Cardiomyocyte formation by skeletal muscle-derived multi-myogenic stem cells after transplantation into infarcted myocardium.PLoS ONE. 2008;3(3):e1789.

[23] 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(9):933-943.

[24] Zhang Y, Liang JL, Wang S, et al. Autologous bone marrow stromal cell trans-plantation with application of granulocyte colony-stimulating factor improves rabbit cardiac performance after acute myocardial infarction. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27(1):43-45, 48.

[25] Wollert KC, Drexler H. Mesenchymal stem cells for myocardial infarction: promises and pitfalls. Circulation. 2005; 112(2):151-153.

[26] Nakamura Y, Wang X, Xu C, et al. Xenotransplantation of Long-Term-Cultured Swine Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cells. 2007;25(3): 612 - 620.

[27] Forte G, Minieri M, Cossa P, et al. Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Am J Physiol Heart Circ Physiol. 2006; 290(4):H1370-1377.

[28] Wang CC, Chen CH, Lin WW, et al. Direct intramyocardial injection of mesenchymal stem cell sheet fragments improves cardiac functions after infarction. Cardiovasc Res. 2008;77: 515-524.

[29] Houtgraaf JH, de Jong R, Kazemi K, et al. Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res. 2013;113(2):153-166.

[30] Rodrigo SF, van Ramshorst J, Hoogslag GE,et al. Intramyocardial injection of autologous bone marrow-derived ex vivo expanded mesenchymal stem cells in acute myocardial infarction patients is feasible and safe up to 5 years of follow-up. J Cardiovasc Transl Res. 2013;6(5): 816-825.

[31] Ishikane S, Hosoda H, Yamahara K,et al. Allogeneic transplantation of fetal membrane-derived mesenchymal stem cell sheets increases neovascularization and improves cardiac function after myocardial infarction in rats. Transplantation. 2013;96(8):697-706.

[32] Vela DC, Silva GV, Assad JAR,et al. Histopathological Study of Healing After Allogenic Mesenchymal Stem Cell Delivery in Myocardial Infarction in Dogs. J Histochem Cytochem. 2009; 57: 167-176.

[33] Ji JF, He BP, Dheen ST,et al. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells. 2004;22(3):415-427.

[34] Chen Y, Ke Q, Yang Y,et al. Cardiomyocytes overexpressing TNF-alpha attract migration of embryonic stem cells via activation of p38 and c-Jun amino-terminal kinase. FASEB J. 2003;17(15):2231-2239.

[35] Kim YS, Park HJ, Hong MH, et al. TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium. Front Biosci. 2009;14:2845-2856.

[36] Honczarenko M, Le Y, Swierkowski M, et al. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells. 2006;24(4): 1030-1041.

[37] Bobis S, Jarocha D, Majka M.Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol. 2006;44(4):215-230.

[38] Zhang M, Mal N, Kiedrowski M, et al. SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J. 2007;21(12): 3197-3207.

[39] Liu X, Duan B, Cheng Z,et al. SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion. Protein Cell. 2011;2(10):845-854.

[40] Xu X, Zhu F, Zhang M,et al. Stromal cell-derived factor-1 enhances wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area and promoting neovascularization. Cells Tissues Organs. 2013;197(2):103-113.

[41] Pasha Z, Wang Y, Sheikh R,et al. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc Res. 2008;77(1):134-142.

[42] Abbott JD, Huang Y, Liu D, et al.Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation. 2004;110(21): 3300-3305.

[43] Zhang D,Huang W,Dai B,et al.Genetically manipulated progenitor cell sheet with diprotin A improves myocardial function and repair of infarcted hearts. Am J Physiol Heart Circ Physiol. 2010;299(5):H1339-1347.

[44] Dong F, Harvey J, Finan A,et al.Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction.Circulation. 2012; 126(3):314-324.