Application of Mesenchymal Stem Cell-derived Cardiomyocytes As Bio-pacemakers: Current Status and Problems to Be Solved

Overview

Journal Med Biol Eng Comput

Publisher Springer

Specialties Biomedical Engineering
Medical Informatics

Date 2007 Jan 31

PMID 17262204

Citations 11

Authors

Yuichi Tomita

Shinji Makino

Daihiko Hakuno

Naoichiro Hattan

Kensuke Kimura

Shunichiro Miyoshi

Mitsushige Murata

Masaki Ieda

Keiichi Fukuda

Affiliations

Soon will be listed here.

Abstract

Bone marrow mesenchymal stem cells (CMG cells) are multipotent and can be induced by 5-azacytidine to differentiate into cardiomyocytes. We characterized the electrophysiological properties of these cardiomyocytes and investigated their potential for use as transplantable bio-pacemakers. After differentiation, action potentials in spontaneously beating cardiomyocytes were initially sinus node-like, but subsequently became ventricular cardiomyocyte-like. RT-PCR established that ion channels mediating I(K1) and I(Kr) were expressed before differentiation. After differentiation, ion channels underlying ICa,L and If were expressed first, followed by ion channels mediating I(to) and I(K,ATP). Differentiated CMG cells expressed beta-adrenergic receptors and increased their beat rate in response to isoproterenol. CMG cardiomyocytes were purified using GFP fluorescence and transplanted into the free walls of the left ventricles of mice. The transplanted cardiomyocytes survived and connected to surrounding recipient cardiomyocytes via intercalated discs. Although further innovation is required, the present findings provide evidence of the potential for bone marrow-derived cardiomyocytes to be used as bio-pacemakers.

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References

Hidaka K, Lee J, Kim H, Ihm C, Iio A, Ogawa M . Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells. FASEB J. 2003; 17(6):740-2. DOI: 10.1096/fj.02-0104fje. View

Maltsev V, Wobus A, Rohwedel J, Bader M, Hescheler J . Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents. Circ Res. 1994; 75(2):233-44. DOI: 10.1161/01.res.75.2.233. View

Eberhardt F, Bode F, Bonnemeier H, Boguschewski F, Schlei M, Peters W . Long term complications in single and dual chamber pacing are influenced by surgical experience and patient morbidity. Heart. 2005; 91(4):500-6. PMC: 1768857. DOI: 10.1136/hrt.2003.025411. View

Wei H, Juhasz O, Li J, Tarasova Y, Boheler K . Embryonic stem cells and cardiomyocyte differentiation: phenotypic and molecular analyses. J Cell Mol Med. 2005; 9(4):804-17. PMC: 6740270. DOI: 10.1111/j.1582-4934.2005.tb00381.x. View

Kuratomi S, Kuratomi A, Kuwahara K, Ishii T, Nakao K, Saito Y . NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes. Biochem Biophys Res Commun. 2006; 353(1):67-73. DOI: 10.1016/j.bbrc.2006.11.119. View

FRIEDENSTEIN A, Chailakhyan R, Gerasimov U . Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet. 1987; 20(3):263-72. DOI: 10.1111/j.1365-2184.1987.tb01309.x. View

Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R, Arbel G . Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol. 2004; 22(10):1282-9. DOI: 10.1038/nbt1014. View

Rozner M, Burton A, Kumar A . Pacemaker complication during magnetic resonance imaging. J Am Coll Cardiol. 2005; 45(1):161-2. DOI: 10.1016/j.jacc.2004.10.004. View

Ferrari G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F . Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998; 279(5356):1528-30. DOI: 10.1126/science.279.5356.1528. View

10.

Rosen M, Robinson R, Brink P, Cohen I . Recreating the biological pacemaker. Anat Rec A Discov Mol Cell Evol Biol. 2004; 280(2):1046-52. DOI: 10.1002/ar.a.20073. View

11.

Itabashi Y, Miyoshi S, Kawaguchi H, Yuasa S, Tanimoto K, Furuta A . A new method for manufacturing cardiac cell sheets using fibrin-coated dishes and its electrophysiological studies by optical mapping. Artif Organs. 2005; 29(2):95-103. DOI: 10.1111/j.1525-1594.2005.29020.x. View

12.

Wahler G . Developmental increases in the inwardly rectifying potassium current of rat ventricular myocytes. Am J Physiol. 1992; 262(5 Pt 1):C1266-72. DOI: 10.1152/ajpcell.1992.262.5.C1266. View

13.

Wetzel G, Klitzner T . Developmental cardiac electrophysiology recent advances in cellular physiology. Cardiovasc Res. 1996; 31 Spec No:E52-60. View

14.

Muller M, Fleischmann B, Selbert S, Ji G, Endl E, Middeler G . Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB J. 2000; 14(15):2540-8. DOI: 10.1096/fj.00-0002com. View

15.

Choate J, Feldman R . Neuronal control of heart rate in isolated mouse atria. Am J Physiol Heart Circ Physiol. 2003; 285(3):H1340-6. DOI: 10.1152/ajpheart.01119.2002. View

16.

Henderson S, Spencer M, Sen A, Kumar C, Siddiqui M, Chien K . Structure, organization, and expression of the rat cardiac myosin light chain-2 gene. Identification of a 250-base pair fragment which confers cardiac-specific expression. J Biol Chem. 1989; 264(30):18142-8. View

17.

Rickard D, Sullivan T, Shenker B, Leboy P, Kazhdan I . Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. Dev Biol. 1994; 161(1):218-28. DOI: 10.1006/dbio.1994.1022. View

18.

Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J . Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999; 103(5):697-705. PMC: 408125. DOI: 10.1172/JCI5298. View

19.

Umezawa A, Maruyama T, Segawa K, Shadduck R, Waheed A, Hata J . Multipotent marrow stromal cell line is able to induce hematopoiesis in vivo. J Cell Physiol. 1992; 151(1):197-205. DOI: 10.1002/jcp.1041510125. View

20.

Hakuno D, Fukuda K, Makino S, Konishi F, Tomita Y, Manabe T . Bone marrow-derived regenerated cardiomyocytes (CMG Cells) express functional adrenergic and muscarinic receptors. Circulation. 2002; 105(3):380-6. DOI: 10.1161/hc0302.102593. View