Sodium channel blockers inhibit the differentiation of rat bone marrow mesenchymal stem cells into cardiac-like cells

doi:10.3969/j.issn.2095-4344.2013.23.001

Abstract

Abstract:

BACKGROUND: The studies have found that the tetrodotoxin-sensitive sodium channels exist in various human and animal mesenchymal stem cells, but whether sodium channels may influence the differentiation of mesenchymal stem cells into myocardial cells has not been confirmed.
OBJECTIVE: To observe the effect of sodium channel blocker tetrodotoxin on the differentiation of mesenchymal stem cells into cardiac-like cells.
METHODS: Rat bone marrow mesenchymal stem cells were isolated with Percoll’s density gradient centrifugation and differential adhesion method, and then the adult rat myocardial cells were isolated by aorta retrograde collagenase perfusion; rat bone marrow mesenchymal stem cells labeled with 4',6-diamidino-2-phenylindole were co-cultured with adult rat myocardial cells, and induced with 0, 10 and 100 μmol/L tetrodotoxin; and then the differentiation of bone marrow mesenchymal stem cells into cardiac-like cells was observed at 1 week after induction.
RESULTS AND CONCLUSION: Immunofluorescence staining showed that the bone marrow mesenchymal stem cells could express cardiac-specific protein desmin and myosin after bone marrow mesenchymal stem cells co-cultured with myocardial cells for 1 week, while 10 and 100 μmol/L tetrodotoxin could inhibit the expressions of desmin and myosin in bone marrow mesenchymal stem cells. The results indicate that sodium channel may play a pivotal role in the differentiation of bone marrow mesenchymal stem cells into cardiac-like cells.

Key words: stem cells, bone marrow-derived stem cells, bone marrow mesenchymal stem cells, myocardial injury, sodium channel, tetrodotoxin, cardiac-like cells, cell differentiation, National Natural Science Foundation of China, stem cell photographs-containing paper

CLC Number:

R394.2

Hao Chun-yuan, Ma Ai-qun, Wang Ting-zhong, Liu Rui. Sodium channel blockers inhibit the differentiation of rat bone marrow mesenchymal stem cells into cardiac-like cells[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(23): 4181-4188.

Figures/Tables 6

References

[1]Taha MF, Valojerdi MR, Mowla SJ. Effect of bone morphogenetic protein-4 (BMP-4) on cardiomyocyte differentiation from mouse embryonic stem cell. Int J Cardiol. 2007;120(1):92-101.

[2]Menasche P. Skeletal muscle satellite cell transplantation. Cardiovasc Res. 2003;58(2):351-357.

[3]Chen M, Xie HQ, Deng L, et al. Stromal cell-derived factor-1 promotes bone marrow-derived cells differentiation to cardiomyocyte phenotypes in vitro. Cell Prolif. 2008; 41(2): 336-347.

[4]Larionov PM, Chernyavskii AM, Kuznetsova IV, et al. Cardiomyocyte regeneration in pericicatricial zone of the myocardium after laser tunneling and implantation of bone marrow mononuclear cells. Bull Exp Biol Med. 2009;148(4): 692-696.

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

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

[7]Xu YL, Gao YH, Liu Z, et al. Myocardium-targeted transplantation of mesenchymal stem cells by diagnostic ultrasound-mediated microbubble destruction improves cardiac function in myocardial infarction of New Zealand rabbits. Int J Cardiol. 2010;138(2):182-195.

[8]Quevedo HC, Hatzistergos KE, Oskouei BN, et al. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci U S A. 2009; 106(33):14022-14027.

[9]Yamahara K, Nagaya N. Mesenchymal stem cells for the treatment of heart disease. Regen Med. 2007;2(2):107-109.

[10]Orlic D. Adult bone marrow stem cells regenerate myocardium in ischemic heart disease. Ann N Y Acad Sci. 2003;996:152-157.

[11]Boyle AJ, Whitbourn R, Schlicht S, et al. Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: a 12-month follow-up. Int J Cardiol. 2006;109 (1): 21-27.

[12]Brenner C, Franz WM. The use of stem cells for the repair of cardiac tissue in ischemic heart disease. Expert Rev Med Devices. 2011;8(2):209-225.

[13]Fuh E, Brinton TJ. Bone marrow stem cells for the treatment of ischemic heart disease: a clinical trial review. J Cardiovasc Transl Res. 2009;2(2):202-218.

[14]Strauer BE, Brehm M, Schannwell CM. The therapeutic potential of stem cells in heart disease. Cell Prolif. 2008;41 Suppl 1:126-145.

[15]Behrends JC. Evolution of the Ion Channel Concept: The Historical Perspective. Chem Rev. In press.

[16]Zaydman MA, Silva JR, Cui J. Ion Channel Associated Diseases: Overview of Molecular Mechanisms. Chem Rev. In press.

[17]Zhang W, Hirschler-Laszkiewicz I, Tong Q, et al. TRPM2 is an ion channel that modulates hematopoietic cell death through activation of caspases and PARP cleavage. Am J Physiol Cell Physiol. 2006;290(4):C1146-1159.

[18]Crozatier B. Central role of PKCs in vascular smooth muscle cell ion channel regulation. J Mol Cell Cardiol. 2006;41(6): 952-955.

[19]Drummond HA, Jernigan NL, Grifoni SC. Sensing tension: epithelial sodium channel/acid-sensing ion channel proteins in cardiovascular homeostasis. Hypertension. 2008;51(5): 1265-1271.

[20]DeCaen PG, Yarov-Yarovoy V, Sharp EM, et al. Sequential formation of ion pairs during activation of a sodium channel voltage sensor. Proc Natl Acad Sci U S A. 2009;106(52): 22498-22503.

[21]Xie Y, Dengler K, Zacharias E, et al. Effects of the sodium channel blocker tetrodotoxin (TTX) on cellular ion homeostasis in rat brain subjected to complete ischemia. Brain Res. 1994;652(2):216-224.

[22]Amaya F, Decosterd I, Samad TA, et al. Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2. Mol Cell Neurosci. 2000;15(4):331-342.

[23]Wu WK, Li GR, Wong TM, et al. Involvement of voltage-gated K+ and Na+ channels in gastric epithelial cell migration. Mol Cell Biochem. 2008;308(1-2):219-226.

[24]Wu WK, Li GR, Wong HP, et al. Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells. J Cell Physiol. 2006;207(2):437-444.

[25]Gao R, Shen Y, Cai J, et al. Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer. Oncol Rep. 2010;23(5):1293-1299.

[26]Mauro T, Guitard M, Behne M, et al. The ENaC channel is required for normal epidermal differentiation. J Invest Dermatol. 2002;118(4):589-594.

[27]Papadatos GA, Wallerstein PM, Head CE, et al. Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a. Proc Natl Acad Sci U S A. 2002;99(9):6210-6215.

[28]Conti CR. Ion channel therapy of ischemic heart disease: from calcium channel blockers to late sodium current inhibition. Clin Cardiol. 2011;34(2):66-67.

[29]Li GR, Deng XL. Functional ion channels in stem cells. World J Stem Cells. 2011;3(3):19-24.

[30]Mareschi K, Rustichelli D, Comunanza V, et al. Multipotent mesenchymal stem cells from amniotic fluid originate neural precursors with functional voltage-gated sodium channels. Cytotherapy. 2009;11(5):534-547.

[31]Li GR, Deng XL, Sun H, et al. Ion channels in mesenchymal stem cells from rat bone marrow. Stem Cells. 2006;24(6): 1519-1528.

[32]Park KS, Jung KH, Kim SH, et al. Functional expression of ion channels in mesenchymal stem cells derived from umbilical cord vein. Stem Cells. 2007;25(8):2044-2052.

[33]Melnikova IN, Gardner PD. The signal transduction pathway underlying ion channel gene regulation by SP1-C-Jun interactions. J Biol Chem. 2001;276(22):19040-19045.

[34]Akbarali HI. Signal-transduction pathways that regulate smooth muscle function. II. Receptor-ion channel coupling mechanisms in gastrointestinal smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2005;288(4):G598-602.

[35]Moore P. Cell biology: ion channels and stem cells. Nature. 2005;438(7068):699-704.

[36]Pillozzi S, Becchetti A. Ion channels in hematopoietic and mesenchymal stem cells. Stem Cells Int. 2012;2012:217910.

[37]Deng XL, Sun HY, Lau CP, et al. Properties of ion channels in rabbit mesenchymal stem cells from bone marrow. Biochem Biophys Res Commun. 2006;348(1):301-309.

[38]Tao R, Lau CP, Tse HF, et al. Functional ion channels in mouse bone marrow mesenchymal stem cells. Am J Physiol Cell Physiol. 2007;293(5):C1561-1567.

[39]Park KS, Choi MR, Jung KH, et al. Diversity of ion channels in human bone marrow mesenchymal stem cells from amyotrophic lateral sclerosis patients. Korean J Physiol Pharmacol. 2008;12(6):337-342.

[40]Maltsev VA, Wobus AM, Rohwedel J, et al. Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents. Circ Res. 1994;75(2):233-244.