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Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells

  • Authors:
    • Yanjun Li
    • Mei Yang
    • Gege Zhang
    • Le Li
    • Bingjie Ye
    • Congxin Huang
    • Yanhong Tang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, Hubei 430060, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 845-851
    |
    Published online on: November 16, 2017
       https://doi.org/10.3892/ijmm.2017.3259
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Abstract

Bone mesenchymal stem cells (BMSCs) are currently considered the optimal stem cells for biological pacemaker cell transformation. The cardiac‑specific transcription factor T‑Box protein 18 (TBX18) is essential for sinoatrial node (SAN) formation, particularly formation of the head region that generates the electrical impulses that induce heart contraction. The present study aimed to confirm the effects of TBX18 on biological pacemaker differentiation of rat BMSCs. Flow cytometry was used to identify the surface markers of BMSCs, in order to acquire pure mesenchymal stem cells. Subsequently, BMSCs were transduced with TBX18 or green fluorescent protein adenovirus vectors. The effects of TBX18 were evaluated using SAN‑specific makers including TBX18, α‑actin, cardiac troponin I, hyperpolarization‑activated cyclic nucleotide‑gated channel 4 and connexin 43 by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunofluorescence. The findings demonstrated that direct conversion of BMSCs to biological pacemaker cells via TBX18 is a feasible method in the field of cardiology.
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1 

Rosen MR: Gene therapy and biological pacing. N Engl J Med. 371:1158–1159. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Chauveau S, Brink PR and Cohen IS: Stem cell-based biological pacemakers from proof of principle to therapy: A review. Cytotherapy. 16:873–880. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Cai B, Li J, Wang J, Luo X, Ai J, Liu Y, Wang N, Liang H, Zhang M, Chen N, et al: microRNA-124 regulates cardiomyocyte differentiation of bone marrow-derived mesenchymal stem cells via targeting STAT3 signaling. Stem Cells. 30:1746–1755. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Psaltis PJ, Zannettino AC, Worthley SG and Gronthos S: Concise review: mesenchymal stromal cells: potential for cardiovascular repair. Stem Cells. 26:2201–2210. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Hamada H, Kobune M, Nakamura K, Kawano Y, Kato K, Honmou O, Houkin K, Matsunaga T and Niitsu Y: Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy. Cancer Sci. 96:149–156. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Zhou YF, Yang XJ, Li HX, Han LH and Jiang WP: Mesenchymal stem cells transfected with HCN2 genes by LentiV can be modified to be cardiac pacemaker cells. Med Hypotheses. 69:1093–1097. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Yang XJ, Zhou YF, Li HX, Han LH and Jiang WP: Mesenchymal stem cells as a gene delivery system to create biological pacemaker cells in vitro. J Int Med Res. 36:1049–1055. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Ma J, Zhang C, Huang S, Wang G and Quan X: Use of rats mesenchymal stem cells modified with mHCN2 gene to create biologic pacemakers. J Huazhong Univ Sci Technolog Med Sci. 30:447–452. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Nong Y, Zhang C, Wei L, Zhang Z, Cheng J, Wen L and Song Z: In situ investigation of allografted mouse HCN4 gene-transfected rat bone marrow mesenchymal stromal cells with the use of patch-clamp recording of ventricular slices. Cytotherapy. 15:905–919. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Wiese C, Grieskamp T, Airik R, Mommersteeg MT, Gardiwal A, de Gier-de Vries C, Schuster-Gossler K, Moorman AF, Kispert A and Christoffels VM: Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res. 104:388–397. 2009. View Article : Google Scholar

11 

McNally EM and Svensson EC: Setting the pace: Tbx3 and Tbx18 in cardiac conduction system development. Circ Res. 104:285–287. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Cho HC: Pacing the heart with genes: Recent progress in biological pacing. Curr Cardiol Rep. 17:652015. View Article : Google Scholar : PubMed/NCBI

13 

Greulich F, Trowe MO, Leffler A, Stoetzer C, Farin HF and Kispert A: Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber-specific developmental programs but does not induce a pacemaker-like gene signature. J Mol Cell Cardiol. 97:140–149. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Kapoor N, Liang W, Marbán E and Cho HC: Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nat Biotechnol. 31:54–62. 2013. View Article : Google Scholar

15 

Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD and Li RK: Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation. 122:2419–2429. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods. 25:402–408. 2001. View Article : Google Scholar

17 

Karaoz E, Aksoy A, Ayhan S, Sariboyaci AE, Kaymaz F and Kasap M: Characterization of mesenchymal stem cells from rat bone marrow: Ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol. 132:533–546. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Ye NS, Chen J, Luo GA, Zhang RL, Zhao YF and Wang YM: Proteomic profiling of rat bone marrow mesenchymal stem cells induced by 5-azacytidine. Stem Cells Dev. 15:665–676. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Tokcaer-Keskin Z, Akar AR, Ayaloglu-Butun F, Terzioglu-Kara E, Durdu S, Ozyurda U, Ugur M and Akcali KC: Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: A perspective for emergencies. Can J Physiol Pharmacol. 87:143–150. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Potapova I, Plotnikov A, Lu Z, Danilo P Jr, Valiunas V, Qu J, Doronin S, Zuckerman J, Shlapakova IN, Gao J, et al: Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res. 94:952–959. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Plotnikov AN, Shlapakova I, Szabolcs MJ, Danilo P Jr, Lorell BH, Potapova IA, Lu Z, Rosen AB, Mathias RT, Brink PR, et al: Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation. 116:706–713. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Cheng J, Zhang Z, Wei L, Nong Y, Wen L, Qin Y and Song Z: Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer create cardiac pacemakers. Cytotherapy. 14:529–539. 2012. View Article : Google Scholar

23 

Wei L, Nong Y, Boli R, Cheng J, Zhang C, Zhou Y and Song Z: mHCN4 genetically modified canine mesenchymal stem cells provide biological pacemaking function in complete dogs with atrioventricular block. Pacing Clin Electrophysiol. 36:1138–1149. 2013. View Article : Google Scholar

24 

Hu YF, Dawkins JF, Cho HC, Marbán E and Cingolani E: Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci Transl Med. 6:245ra942014. View Article : Google Scholar : PubMed/NCBI

25 

Takahashi-Yanaga F, Morimoto S, Harada K, Minakami R, Shiraishi F, Ohta M, Lu QW, Sasaguri T and Ohtsuki I: Functional consequences of the mutations in human cardiac troponin I gene found in familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 33:2095–2107. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Ruan Z, Zhu L, Yin Y and Chen G: Overexpressing NKx2.5 increases the differentiation of human umbilical cord drived mesenchymal stem cells into cardiomyocyte-like cells. Biomed Pharmacother. 78:110–115. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Xu M, Wani M, Dai YS, Wang J, Yan M, Ayub A and Ashraf M: Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes. Circulation. 110:2658–2665. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Husse B and Franz WM: Generation of cardiac pacemaker cells by programming and differentiation. Biochim Biophys Acta. 1948–1952.2016:1863PubMed/NCBI

29 

Robinson RB and Siegelbaum SA: Hyperpolarization-activated cation currents: From molecules to physiological function. Annu Rev Physiol. 65:453–480. 2003. View Article : Google Scholar

30 

Verkerk AO and Wilders R: Pacemaker activity of the human sinoatrial node: Effects of HCN4 mutations on the hyperpolarization-activated current. Europace. 16:384–395. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Kapoor N, Galang G, Marbán E and Cho HC: Transcriptional suppression of connexin43 by TBX18 undermines cell-cell electrical coupling in postnatal cardiomyocytes. J Biol Chem. 286:14073–14079. 2011. View Article : Google Scholar : PubMed/NCBI

32 

French BA, Mazur W, Geske RS and Bolli R: Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation. 90:2414–2424. 1994. View Article : Google Scholar : PubMed/NCBI

33 

Brenner M: Gene transfer by adenovectors. Blood. 94:3965–3967. 1999.PubMed/NCBI

34 

Wright MJ, Wightman LM, Lilley C, de Alwis M, Hart SL, Miller A, Coffin RS, Thrasher A, Latchman DS and Marber MS: In vivo myocardial gene transfer: Optimization, evaluation and direct comparison of gene transfer vectors. Basic Res Cardiol. 96:227–236. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Li RA: Gene- and cell-based bio-artificial pacemaker: What basic and translational lessons have we learned? Gene Ther. 19:588–595. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Yang M, Zhang G, Li L, Ye B, Huang C and Tang Y: Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells. Int J Mol Med 41: 845-851, 2018.
APA
Li, Y., Yang, M., Zhang, G., Li, L., Ye, B., Huang, C., & Tang, Y. (2018). Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells. International Journal of Molecular Medicine, 41, 845-851. https://doi.org/10.3892/ijmm.2017.3259
MLA
Li, Y., Yang, M., Zhang, G., Li, L., Ye, B., Huang, C., Tang, Y."Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells". International Journal of Molecular Medicine 41.2 (2018): 845-851.
Chicago
Li, Y., Yang, M., Zhang, G., Li, L., Ye, B., Huang, C., Tang, Y."Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells". International Journal of Molecular Medicine 41, no. 2 (2018): 845-851. https://doi.org/10.3892/ijmm.2017.3259
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Yang M, Zhang G, Li L, Ye B, Huang C and Tang Y: Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells. Int J Mol Med 41: 845-851, 2018.
APA
Li, Y., Yang, M., Zhang, G., Li, L., Ye, B., Huang, C., & Tang, Y. (2018). Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells. International Journal of Molecular Medicine, 41, 845-851. https://doi.org/10.3892/ijmm.2017.3259
MLA
Li, Y., Yang, M., Zhang, G., Li, L., Ye, B., Huang, C., Tang, Y."Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells". International Journal of Molecular Medicine 41.2 (2018): 845-851.
Chicago
Li, Y., Yang, M., Zhang, G., Li, L., Ye, B., Huang, C., Tang, Y."Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell differentiation to biological pacemaker cells". International Journal of Molecular Medicine 41, no. 2 (2018): 845-851. https://doi.org/10.3892/ijmm.2017.3259
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