Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
August-2017 Volume 40 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2017 Volume 40 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro

  • Authors:
    • Xiaobin Ni
    • Caiwen Ou
    • Jingbin Guo
    • Bei Liu
    • Jianwu Zhang
    • Zhiye Wu
    • Hekai Li
    • Minsheng Chen
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
    Copyright: © Ni et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 418-426
    |
    Published online on: June 12, 2017
       https://doi.org/10.3892/ijmm.2017.3019
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial growth factor (VEGF) and B‑cell lymphoma‑2 (Bcl‑2) confers a higher expression level of the target genes, better survival and a stronger paracrine effect in MSCs in an adverse environment than the modification of the individual genes. For this purpse, a lentiviral vector was constructed by using a self‑cleaving T2A peptide sequence to link and achieve the co‑overexpression of VEGF and Bcl‑2. Rat MSCs were transfected to obtain cell lines that exhibited a stable overexpression. An in vitro model of oxygen glucose deprivation (OGD) was applied to mimic the ischemic microenvironment, and cell apoptosis, autophagy and the paracrine effects were then determined. Compared with the MSCs in which individual genes were modified and the control MSCs, the MSCs which were subjected to dual genetic modification had a higher expression level of the target genes, a more rapid proliferation, reduced apoptosis, decreased autophagy and an enhanced paracrine effect. Furthermore, the suppression of autophagy was found to contribute to the inhibition of apoptosis in this in vitro OGD model. On the whole, these data indicate that the co‑overexpression of VEGF and Bcl‑2 protects MSCs in an ischemic environment by inhibiting apoptosis, suppressing autophagy and enhancing the paracrine effects.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Wang X, Zhang J, Zhang F, Li J, Li Y, Tan Z, Hu J, Qi Y, Li Q and Yan B: The clinical status of stem cell therapy for ischemic cardiomyopathy. Stem Cells Int. 2015:1350232015. View Article : Google Scholar : PubMed/NCBI

2 

Wang XJ and Li QP: The roles of mesenchymal stem cells (MSCs) therapy in ischemic heart diseases. Biochem Biophys Res Commun. 359:189–193. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Duran JM, Makarewich CA, Sharp TE, Starosta T, Zhu F, Hoffman NE, Chiba Y, Madesh M, Berretta RM, Kubo H, et al: Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms. Circ Res. 113:539–552. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Young PP and Schäfer R: Cell-based therapies for cardiac disease: A cellular therapist's perspective. Transfusion. 55:441–451; quiz 440. 2015. View Article : Google Scholar

5 

Lee S, Choi E, Cha MJ and Hwang KC: Cell adhesion and long-term survival of transplanted mesenchymal stem cells: A prerequisite for cell therapy. Oxid Med Cell Longev. 2015:6329022015. View Article : Google Scholar : PubMed/NCBI

6 

Penn MS and Mangi AA: Genetic enhancement of stem cell engraftment, survival, and efficacy. Circ Res. 102:1471–1482. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Matsumoto R, Omura T, Yoshiyama M, Hayashi T, Inamoto S, Koh KR, Ohta K, Izumi Y, Nakamura Y, Akioka K, et al: Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction. Arterioscler Thromb Vasc Biol. 25:1168–1173. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Li W, Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, Furlani D, Piechaczek C, Moebius JM, Lützow K, et al: Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells. 25:2118–2127. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Baek JH, Jang JE, Kang CM, Chung HY, Kim ND and Kim KW: Hypoxia-induced VEGF enhances tumor survivability via suppression of serum deprivation-induced apoptosis. Oncogene. 19:4621–4631. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Wang D, Weng Q, Zhang L, He Q and Yang B: VEGF and Bcl-2 interact via MAPKs signaling pathway in the response to hypoxia in neuroblastoma. Cell Mol Neurobiol. 29:391–401. 2009. View Article : Google Scholar

11 

Shearer RF and Saunders DN: Experimental design for stable genetic manipulation in mammalian cell lines: Lentivirus and alternatives. Genes Cells. 20:1–10. 2015. View Article : Google Scholar

12 

Sakuma T, Barry MA and Ikeda Y: Lentiviral vectors: Basic to translational. Biochem J. 443:603–618. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Ibrahimi A, Vande Velde G, Reumers V, Toelen J, Thiry I, Vandeputte C, Vets S, Deroose C, Bormans G, Baekelandt V, et al: Highly efficient multicistronic lentiviral vectors with peptide 2A sequences. Hum Gene Ther. 20:845–860. 2009. View Article : Google Scholar : PubMed/NCBI

14 

McGinley LM, McMahon J, Stocca A, Duffy A, Flynn A, O'Toole D and O'Brien T: Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression. Hum Gene Ther. 24:840–851. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Wang X, Zhao T, Huang W, Wang T, Qian J, Xu M, Kranias EG, Wang Y and Fan GC: Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells. 27:3021–3031. 2009.PubMed/NCBI

16 

Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS and Dzau VJ: Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 9:1195–1201. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Fan L, Lin C, Zhuo S, Chen L, Liu N, Luo Y, Fang J, Huang Z, Lin Y and Chen J: Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction. Eur J Heart Fail. 11:1023–1030. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Tang YL, Zhao Q, Qin X, Shen L, Cheng L, Ge J and Phillips MI: Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg. 80:229–237. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Banai S, Jaklitsch MT, Shou M, Lazarous DF, Scheinowitz M, Biro S, Epstein SE and Unger EF: Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation. 89:2183–2189. 1994. View Article : Google Scholar : PubMed/NCBI

20 

Deuse T, Peter C, Fedak PW, Doyle T, Reichenspurner H, Zimmermann WH, Eschenhagen T, Stein W, Wu JC, Robbins RC, et al: Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation. 120(Suppl 11): S247–S254. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Locatelli P, Olea FD, Hnatiuk A, De Lorenzi A, Cerdá M, Giménez CS, Sepúlveda D, Laguens R and Crottogini A: Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction. Gene Ther. 22:449–457. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Jiang S, Haider HK, Idris NM, Salim A and Ashraf M: Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyo-genesis for cardiac repair. Circ Res. 99:776–784. 2006. View Article : Google Scholar : PubMed/NCBI

23 

McMahon JM, Conroy S, Lyons M, Greiser U, O'shea C, Strappe P, Howard L, Murphy M, Barry F and O'Brien T: Gene transfer into rat mesenchymal stem cells: A comparative study of viral and nonviral vectors. Stem Cells Dev. 15:87–96. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Lindqvist LM and Vaux DL: BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy. Autophagy. 10:1474–1475. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Boya P, González-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Métivier D, Meley D, Souquere S, Yoshimori T, et al: Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol. 25:1025–1040. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Denton D, Xu T and Kumar S: Autophagy as a pro-death pathway. Immunol Cell Biol. 93:35–42. 2015. View Article : Google Scholar

27 

Fitzwalter BE and Thorburn A: Recent insights into cell death and autophagy. FEBS J. 282:4279–4288. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Haider HK, Jiang S, Idris NM and Ashraf M: IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair. Circ Res. 103:1300–1308. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Fiedler J, Brill C, Blum WF and Brenner RE: IGF-I and IGF-II stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells. Biochem Biophys Res Commun. 345:1177–1183. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Song H, Song BW, Cha MJ, Choi IG and Hwang KC: Modification of mesenchymal stem cells for cardiac regeneration. Expert Opin Biol Ther. 10:309–319. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ni X, Ou C, Guo J, Liu B, Zhang J, Wu Z, Li H and Chen M: Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro. Int J Mol Med 40: 418-426, 2017.
APA
Ni, X., Ou, C., Guo, J., Liu, B., Zhang, J., Wu, Z. ... Chen, M. (2017). Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro. International Journal of Molecular Medicine, 40, 418-426. https://doi.org/10.3892/ijmm.2017.3019
MLA
Ni, X., Ou, C., Guo, J., Liu, B., Zhang, J., Wu, Z., Li, H., Chen, M."Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro". International Journal of Molecular Medicine 40.2 (2017): 418-426.
Chicago
Ni, X., Ou, C., Guo, J., Liu, B., Zhang, J., Wu, Z., Li, H., Chen, M."Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro". International Journal of Molecular Medicine 40, no. 2 (2017): 418-426. https://doi.org/10.3892/ijmm.2017.3019
Copy and paste a formatted citation
x
Spandidos Publications style
Ni X, Ou C, Guo J, Liu B, Zhang J, Wu Z, Li H and Chen M: Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro. Int J Mol Med 40: 418-426, 2017.
APA
Ni, X., Ou, C., Guo, J., Liu, B., Zhang, J., Wu, Z. ... Chen, M. (2017). Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro. International Journal of Molecular Medicine, 40, 418-426. https://doi.org/10.3892/ijmm.2017.3019
MLA
Ni, X., Ou, C., Guo, J., Liu, B., Zhang, J., Wu, Z., Li, H., Chen, M."Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro". International Journal of Molecular Medicine 40.2 (2017): 418-426.
Chicago
Ni, X., Ou, C., Guo, J., Liu, B., Zhang, J., Wu, Z., Li, H., Chen, M."Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro". International Journal of Molecular Medicine 40, no. 2 (2017): 418-426. https://doi.org/10.3892/ijmm.2017.3019
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team