Transplantation of human umbilical cord mesenchymal stem cells derived at different gestational weeks improves heart function in myocardial infarction models

doi:10.3969/j.issn.2095-4344.2016.06.006

Abstract

Abstract:

BACKGROUND: Stem cells have multi-directional differentiation and self-replication abilities, under certain conditions, which can differentiate into myocardial cells to repair the damaged myocardium.
OBJECTIVE: To investigate the effects of transplantation of umbilical cord mesenchymal stem cells derived at different gestational weeks on infarct size and angiogenesis in the infarct region of experimental rabbits with myocardial infarction.
METHODS: Ten full-term umbilical cord samples and 10 umbilical cord samples of aborted fetuses at 10-12 gestation weeks were selected to in vitro isolate umbilical cord mesenchymal stem cells that were subjected to BrdU labeling. HLA-G expression was detected in the cells. Thirty white rabbits were selected to make myocardial infarction models, and 2 weeks after modeling, the model rabbits were randomized into aborted cell transplantation group, full-term cell transplantation group and control group (n=10 per group). Then, BrdU-labeled cells were injected correspondingly into the infarct region of rabbits in the two cell transplantation groups. Rabbits in the control group were subjected to an equal volume of serum-free. Four weeks after transplantation, heart function of rabbits was monitored using electrocardiogram, and myocardial tissues were taken to measure infarct size and blood capillary density.
RESULTS AND CONCLUSION: HLA-G expression was different in different sources of umbilical cord mesenchymal stem cells: high HLA-G expression was found in the aborted umbilical cord mesenchymal stem cells, and meanwhile, low HLA-G expression was found in the full-term umbilical cord mesenchymal stem cells. Compared with the control group, the left ventricular end-diastolic volume and left ventricular ejection fraction of aborted and full-term cell transplantation groups were significantly improved, especially in the aborted cell transplantation group (P < 0.05). BrdU-positive cells were found in the infarct site in both transplantation groups. Compared with the control group, the infarct size and capillary density were improved most significantly in the aborted cell transplantation group followed by the full-term cell transplantation group (P < 0.05). Electrocardiogram findings showed significant improvement in both cell transplantation groups compared with the control group (P < 0.05), especially in the aborted cell transplantation group. These findings indicate that umbilical cord mesenchymal stem cells derived at low gestational weeks improve the heart function more significantly than the full-term umbilical cord mesenchymal stem cells, which have the potential to become a better source of cardiomyocytes for transplantation.

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

Wang Wei, Li Xiao-fu, Li Zhong-jian. Transplantation of human umbilical cord mesenchymal stem cells derived at different gestational weeks improves heart function in myocardial infarction models[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(6): 799-806.

Figures/Tables 3

References

[1] Soonpaa MH, Koh GY, Klug MG,et al.Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium.Science. 1994 Apr 1;264(5155):98-101.
[2] Orlic D, Kajstura J, Chimenti S,et al.Bone marrow cells regenerate infarcted myocardium.Nature. 2001;410 (6829):701-705.
[3] Kamdar F, Jameel MN, Score P, et al. Cellular therapy promotes endogenous stem cell repair.Can J Physiol Pharmacol. 2012;90(10):1335-1344.
[4] Mohsin S, Khan M, Toko H,et al.Human cardiac progenitor cells engineered with Pim-I kinase enhance myocardial repair.J Am Coll Cardiol. 2012;60(14): 1278-1287.
[5] Bolli R, Tang XL, Sanganalmath SK,et al.Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy.Circulation. 2013;128(2):122-131.
[6] 牛红星,穆军升,张健群,等.骨髓间充质干细胞向心肌分化的实验研究[J].心肺血管病杂志,2013,32(3): 357-360.
[7] 张颖,李娜,辛毅,等.大鼠静脉注射人脐带胶样组织来源间充质干细胞的安全性研究[J].心肺血管病杂志,2013,32 (6):783-788.
[8] 李娜,辛毅,林筝,等.多次移植人脐带间充质干细胞对大鼠Th1和Th2比值的影响[J].心肺血管病杂志,2013,32(6): 789-793.
[9] Strauer BE, Brehm M, Zeus T, et al. Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr. 2001;126(34-35):932-938.
[10] Assmus B, Schächinger V, Teupe C, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002;106(24):3009-3017.
[11] Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361(9351):45-46.
[12] Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364(9429):141-148.
[13] Donndorf P, Kundt G, Kaminski A, et al. Intramyocardial bone marrow stem cell transplantation during coronary artery bypass surgery: a meta-analysis. J Thorac Cardiovasc Surg. 2011;142(4):911-920.
[14] Chugh AR, Beache GM, Loughran JH, et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012;126(11 Suppl 1):S54-64.
[15] Bartunek J, Behfar A, Dolatabadi D, et al. Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol. 2013;61(23):2329-2338.
[16] Fisher SA, Dorée C, Brunskill SJ, et al. Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis. PLoS One. 2013;8(6):e64669.
[17] Kandala J, Upadhyay GA, Pokushalov E, et al. Meta-analysis of stem cell therapy in chronic ischemic cardiomyopathy. Am J Cardiol. 2013;112(2):217-225.
[18] 姚艳,杜昕,马长生.骨髓间充质干细胞治疗缺血性心脏病的机制和应用[J].心肺血管病杂志,2014,33(3):460-463.
[19] 李娜,孔晴宇,辛毅,等.间充质干细胞治疗心肌缺血性疾病的临床研究进展[J].心肺血管病杂志,2013,32(3):377- 379.
[20] Friedenstein AJ, Petrakova KV, Kurolesova AI, et al. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6(2):230-247.
[21] Awad HA, Butler DL, Boivin GP, et al. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng. 1999;5(3):267-277.
[22] Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-317.
[23] 郭子宽.间充质干细胞及其临床应用中的几个问题[J].中国组织工程研究,2012,16(1):1-10.
[24] 牟乐明,孙占胜,王伯珉,等.骨髓间充质干细胞移植对脊髓损伤大鼠Toll样受体4表达的影响[J].山东大学学报:医学版.2014,52(1):37-41.
[25] Nagaya N, Kangawa K, Itoh T, et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 2005;112(8):1128-1135.
[26] 王建安,谢小洁,何红,等.骨髓间质干细胞移植治疗原发性扩张型心肌病的疗效与安全性[J].中华心血管病杂志, 2006,34(2):107-110.
[27] Yang CC, Shih YH, Ko MH, et al. Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. PLoS One. 2008;3(10):e3336.
[28] Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis. Liver Transpl. 2009;15(5):484-495.
[29] Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42-48.
[30] Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99(10):3838-3843.
[31] Glennie S, Soeiro I, Dyson PJ, et al. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005;105(7): 2821-2827.
[32] Le Blanc K. Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy. 2003; 5(6):485-489.
[33] Xiong Q, Ye L, Zhang P, et al. Functional consequences of human induced pluripotent stem cell therapy: myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling. Circulation. 2013;127(9):997-1008.
[34] Malliaras K, Zhang Y, Seinfeld J, et al. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med. 2013;5(2): 191-209.
[35] Lila N, Amrein C, Guillemain R, et al. Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection. Circulation. 2002;105(16):1949-1954.
[36] Marchal-Bras-Goncalves R, Rouas-Freiss N, Connan F, et al. A soluble HLA-G protein that inhibits natural killer cell-mediated cytotoxicity. Transplant Proc. 2001; 33(3):2355-2359.
[37] Horuzsko A, Lenfant F, Munn DH, et al. Maturation of antigen-presenting cells is compromised in HLA-G transgenic mice. Int Immunol. 2001;13(3):385-394.
[38] Ristich V, Liang S, Zhang W, et al. Tolerization of dendritic cells by HLA-G. Eur J Immunol. 2005;35(4): 1133-1142.
[39] Liang S, Baibakov B, Horuzsko A. HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor. Eur J Immunol. 2002;32(9): 2418-2426.
[40] Kanai T, Fujii T, Unno N, et al. Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood. Am J Reprod Immunol. 2001;45(2):94-99.
[41] Lila N, Carpentier A, Amrein C, et al. Implication of HLA-G molecule in heart-graft acceptance .Lancet. 2000;355(9221):2138.
[42] Qiu J, Terasaki PI, Miller J, et al. Soluble HLA-G expression and renal graft acceptance. Am J Transplant. 2006;6(9):2152-2156.
[43] Luque J, Torres MI, Aumente MD, et al. Soluble HLA-G in heart transplantation: their relationship to rejection episodes and immunosuppressive therapy. Hum Immunol. 2006;67(4-5):257-263.