Skip to main content
SpringerLink
Log in

Human menstrual blood–derived stem cells protect H9c2 cells against hydrogen peroxide–associated apoptosis

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Human menstrual blood–derived mesenchymal stem cells (MenSCs) hold great promise for regenerative medicine. Here, H2O2-associated damage in H9c2 cells was employed as an in vitro ischemia–reperfusion model, and the transwell system was used to explore the beneficial effects of MenSCs on the H2O2-induced damage of myocardial H9c2 cells. H2O2 treatment resulted in decreased viability and migration rate, with increased apoptosis levels in cells. By contrast, upon co-culture with MenSCs, H9c2 cell viability and migration were increased, whereas the apoptotic rate decreased. Additionally, western blot and qRT-PCR showed that MenSCs mediated the anti-apoptotic role by downregulating the pro-apoptotic genes Bax and caspase-3, while upregulating the anti-apoptotic effector Bcl-2. Furthermore, co-culture with MenSCs resulted in elevated expression of N-cadherin after H2O2 treatment. These findings indicate that MenSCs protect H9c2 cells against H2O2-associated programmed cell death and would help develop therapeutic tools for cardiomyocyte apoptosis associated with oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326

    Article  CAS  PubMed  Google Scholar 

  • Anderson JL, Morrow DA (2017) Acute myocardial infarction. N Engl J Med 376:2053–2064

    Article  CAS  PubMed  Google Scholar 

  • Bockeria L, Bogin V, Bockeria O, Le T, Alekyan B, Woods EJ, Brown AA, Ichim TE, Patel AN (2013) Endometrial regenerative cells for treatment of heart failure: a new stem cell enters the clinic. J Transl Med 11:56

    Article  PubMed  PubMed Central  Google Scholar 

  • Borlongan CV, Kaneko Y, Maki M, Yu SJ, Ali M, Allickson JG, Sanberg CD, Kuzmin-Nichols N, Sanberg PR (2010) Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke. Stem Cells Dev 19:439–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ (2001) BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8:705–711

    Article  CAS  PubMed  Google Scholar 

  • De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, Pascual CY, Aller MA, Arias J, Arnalich-Montiel F (2012) Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 12:574–591

    Article  PubMed  Google Scholar 

  • Desagher S, Martinou JC (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol 10:369–377

    Article  CAS  PubMed  Google Scholar 

  • Fatkhudinov T, Bolshakova G, Arutyunyan I, Elchaninov A, Makarov A, Kananykhina E, Khokhlova O, Murashev A, Glinkina V, Goldshtein D (2015) Bone marrow-derived multipotent stromal cells promote myocardial fibrosis and reverse remodeling of the left ventricle. Stem Cells Int 2015:746873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Forouzanfar MH, Moran AE, Flaxman AD, Roth G, Mensah GA, Ezzati M, Naghavi M, Murray CJ (2012) Assessing the global burden of ischemic heart disease, part 2: analytic methods and estimates of the global epidemiology of ischemic heart disease in 2010. Glob Heart 7:331–342

    Article  PubMed  Google Scholar 

  • Fu Y, Karbaat L, Wu L, Leijten J, Both SK, Karperien M (2017) Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng B Rev 23:515–528

    Article  CAS  Google Scholar 

  • Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell 147:742–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G (2006) Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 13:1423–1433

    Article  CAS  PubMed  Google Scholar 

  • Gavert N, Ben-Ze'ev A (2008) Epithelial-mesenchymal transition and the invasive potential of tumors. Trends Mol Med 14:199–209

    Article  CAS  PubMed  Google Scholar 

  • Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115:500–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gustafsson AB, Gottlieb RA (2003) Mechanisms of apoptosis in the heart. J Clin Immunol 23:447–459

    Article  CAS  PubMed  Google Scholar 

  • Hohensinner PJ, Takacs N, Kaun C, Thaler B, Krychtiuk KA, Pfaffenberger S, Aliabadi A, Zuckermann A, Huber K, Wojta J (2017) Urokinase plasminogen activator protects cardiac myocytes from oxidative damage and apoptosis via hOGG1 induction. Apoptosis 22:1048–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imanishi Y, Saito A, Komoda H, Kitagawa-Sakakida S, Miyagawa S, Kondoh H, Ichikawa H, Sawa Y (2008) Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats. J Mol Cell Cardiol 44:662–671

    Article  CAS  PubMed  Google Scholar 

  • Khanmohammadi M, Khanjani S, Edalatkhah H, Zarnani AH, Heidari-Vala H, Soleimani M, Alimoghaddam K, Kazemnejad S (2014) Modified protocol for improvement of differentiation potential of menstrual blood-derived stem cells into adipogenic lineage. Cell Prolif 47:615–623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovecsi A, Gurzu S, Szentirmay Z, Kovacs Z, Bara TJ, Jung I (2017) Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/glycoprotein A34 in gastrointestinal stromal tumors. World J Gastrointest Oncol 9:436–443

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee Y, Gustafsson AB (2009) Role of apoptosis in cardiovascular disease. Apoptosis 14:536–548

    Article  PubMed  Google Scholar 

  • Lv Y, Xu X, Zhang B, Zhou G, Li H, Du C, Han H, Wang H (2014) Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice. J Transl Med 12:344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng X, Ichim TE, Zhong J, Rogers A, Yin Z, Jackson J, Wang H, Ge W, Bogin V, Chan KW (2007) Endometrial regenerative cells: a novel stem cell population. J Transl Med 5:57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mothe AJ, Tator CH (2012) Advances in stem cell therapy for spinal cord injury. J Clin Invest 122:3824–3834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy MP, Wang H, Patel AN, Kambhampati S, Angle N, Chan K, Marleau AM, Pyszniak A, Carrier E, Ichim TE (2008) Allogeneic endometrial regenerative cells: an “off the shelf solution” for critical limb ischemia? J Transl Med 6:45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nadanaka S, Kinouchi H, Kitagawa H (2018) Chondroitin sulfate-mediated N-cadherin/beta-catenin signaling is associated with basal-like breast cancer cell invasion. J Biol Chem 293:444–465

    Article  CAS  PubMed  Google Scholar 

  • Patel AN, Park E, Kuzman M, Benetti F, Silva FJ, Allickson JG (2008) Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transplant 17:303–311

    Article  PubMed  Google Scholar 

  • Rosdah AA, Bond ST, Sivakumaran P, Hoque A, Oakhill JS, Drew BG, Delbridge LMD, Lim SY (2017) Mdivi-1 protects human W8B2(+) cardiac stem cells from oxidative stress and simulated ischemia-reperfusion injury. Stem Cells Dev 26:1771–1780

    Article  CAS  PubMed  Google Scholar 

  • Scarabelli TM, Stephanou A, Pasini E, Comini L, Raddino R, Knight RA, Latchman DS (2002) Different signaling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischemia/reperfusion injury. Circ Res 90:745–748

    Article  CAS  PubMed  Google Scholar 

  • Sharikabad MN, Ostbye KM, Brors O (2004) Effect of hydrogen peroxide on reoxygenation-induced Ca2+ accumulation in rat cardiomyocytes. Free Radic Biol Med 37:531–538

    Article  CAS  PubMed  Google Scholar 

  • Soleymaninejadian E, Pramanik K, Samadian E (2012) Immunomodulatory properties of mesenchymal stem cells: cytokines and factors. Am J Reprod Immunol 67:1–8

    Article  CAS  PubMed  Google Scholar 

  • Song N, Zhong J, Hu Q, Gu T, Yang B, Zhang J, Yu J, Ma X, Chen Q, Qi J (2018) FGF18 enhances migration and the epithelial-mesenchymal transition in breast cancer by regulating Akt/GSK3beta/beta-catenin signaling. Cell Physiol Biochem 49:1019–1032

    Article  CAS  PubMed  Google Scholar 

  • Toldo S, Breckenridge DG, Mezzaroma E, Van Tassell BW, Shryock J, Kannan H, Phan D, Budas G, Farkas D, Lesnefsky E (2012) Inhibition of apoptosis signal-regulating kinase 1 reduces myocardial ischemia-reperfusion injury in the mouse. J Am Heart Assoc 1:e002360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trounson A, McDonald C (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17:11–22

    Article  CAS  PubMed  Google Scholar 

  • von Harsdorf R, Li PF, Dietz R (1999) Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation 99:2934–2941

    Article  Google Scholar 

  • Watkins SJ, Borthwick GM, Arthur HM (2011) The H9C2 cell line and primary neonatal cardiomyocyte cells show similar hypertrophic responses in vitro. In Vitro Cell Dev Biol Anim 47:125–131

    Article  CAS  PubMed  Google Scholar 

  • Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, Shirani J, Armstrong RC, Kitsis RN (2003) A mechanistic role for cardiac myocyte apoptosis in heart failure. J Clin Invest 111:1497–1504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Luo Y, Chen J, Pan R, Xiang B, Du X, Xiang L, Shao J, Xiang C (2014) Transplantation of human menstrual blood progenitor cells improves hyperglycemia by promoting endogenous progenitor differentiation in type 1 diabetic mice. Stem Cells Dev 23:1245–1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan X, Yan L, Liu S, Shan Z, Tian Y, Jin Z (2015) N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer. Mol Med Rep 12:2999–3006

    Article  CAS  PubMed  Google Scholar 

  • Youn SW, Lee HC, Lee SW, Lee J (2018) COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation. Sci Rep 8:12323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Wang K, Lei Y, Li Q, Nice EC, Huang C (2015) Redox signaling: potential arbitrator of autophagy and apoptosis in therapeutic response. Free Radical Biol Med 89:452–465

    Article  CAS  Google Scholar 

  • Zhao L, Yang G, Zhao X (2014) Rho-associated protein kinases play an important role in the differentiation of rat adipose-derived stromal cells into cardiomyocytes in vitro. PLoS One 9:e115191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu GJ, Song PP, Zhou H, Shen XH, Wang JG, Ma XF, Gu YJ, Liu DD, Feng AN, Qian XY (2018) Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, beta-catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol Lett 15:3472–3481

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by Nantong Science and Technology Project (MS22016030), the National Natural Science Foundation of China (81501189), and Jiangsu Government Scholarship for Overseas Studies (JS-2016-061).

Author information

Author notes

  1. Song Chen and Chuanming Dong contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Nantong Maternal and Child Health Care Hospital, No. 399 Century Avenue, Nantong, 226001, Jiangsu, China

    Song Chen, Jinyun Zhang, Baohua Tang & Jian Chen

  2. Department of Anatomy, Medical School of Nantong University, Laboratory Animal Center of Nantong University, Nantong, 226001, Jiangsu, China

    Chuanming Dong & Qinghua Wang

  3. Department of Emergency, Nantong Maternal and Child Health Care Hospital, Nantong, Jiangsu, China

    Zhengrong Xi

  4. Department of Cardiology, Nantong Third People’s Hospital, Nantong, Jiangsu, China

    Fei Cai

  5. Department of Geriatric Medicine, Nantong Third People’s Hospital, Nantong, Jiangsu, China

    Yachi Gong

  6. Department of Emergency, Nantong Third People’s Hospital, Nantong, Jiangsu, China

    Jianru Xu

  7. Department of Interventional Therapy, Nantong Third People’s Hospital, Nantong, Jiangsu, China

    Longju Qi

Authors
  1. Song Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chuanming Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinyun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Baohua Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhengrong Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fei Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yachi Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jianru Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Longju Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qinghua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qinghua Wang or Jian Chen.

Ethics declarations

All procedures were performed after informed consent provision by the volunteers, with approval from the Ethics Committee of Nantong Maternal and Child Health Care Hospital, affiliated to Nantong University, China (license no. is 2016-023).

Additional information

Editor: Tetsuji Okamoto

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Dong, C., Zhang, J. et al. Human menstrual blood–derived stem cells protect H9c2 cells against hydrogen peroxide–associated apoptosis. In Vitro Cell.Dev.Biol.-Animal 55, 104–112 (2019). https://doi.org/10.1007/s11626-018-0311-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-018-0311-1

Keywords

Search

Navigation