Abstract
Regenerative therapies, including cell injection and bioengineered tissue transplantation, have the potential to treat severe heart failure. Direct implantation of isolated skeletal myoblasts and bone-marrow-derived cells has already been clinically performed and research on fabricating three-dimensional (3-D) cardiac grafts using tissue engineering technologies has also now been initiated. In contrast to conventional scaffold-based methods, we have proposed cell sheet-based tissue engineering, which involves stacking confluently cultured cell sheets to construct 3-D cell-dense tissues. Upon layering, individual cardiac cell sheets integrate to form a single, continuous, cell-dense tissue that resembles native cardiac tissue. The transplantation of layered cardiac cell sheets is able to repair damaged hearts. As the next step, we have attempted to promote neovascularization within bioengineered myocardial tissues to overcome the longstanding limitations of engineered tissue thickness. Finally, as a possible advanced therapy, we are now trying to fabricate functional myocardial tubes that may have a potential for circulatory support. Cell sheet-based tissue engineering technologies therefore show an enormous promise as a novel approach in the field of myocardial tissue engineering.
Similar content being viewed by others
References
Birla RK, Dow DE, Huang YC, Migneco F, Khait L, Borschel GH, Dhawan V, Brown DL (2008) Methodology for the formation of functional, cell-based cardiac pressure generation constructs in vitro. In Vitro Cell Dev Biol Anim 44:340–350
Christman KL, Lee RJ (2006) Biomaterials for the treatment of myocardial infarction. J Am Coll Cardiol 48:907–913
Dai W, Wold LE, Dow JS, Kloner RA (2005) Thickening of the infarcted wall by collagen injection improves left ventricular function in rats: A novel approach to preserve cardiac function after myocardial infarction. J Am Coll Cardiol 46:714–719
Evans HJ, Sweet JK, Price RL, Yost M, Goodwin RL (2003) Novel 3 d culture system for study of cardiac myocyte development. Am J Physiol Heart Circ Physiol 285:H570–H578
Fink C, Ergun S, Kralisch D, Remmers U, Weil J, Eschenhagen T (2000) Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement. FASEB J 14:669–679
Haraguchi Y, Shimizu T, Yamato M, Kikuchi A, Okano T (2006) Electrical coupling of cardiomyocyte sheets occurs rapidly via functional gap junction formation. Biomaterials 27:4765–4774
Hasegawa M, Yamato M, Kikuchi A, Okano T, Ishikawa I (2005) Human periodontal ligament cell sheets can regenerate periodontal ligament tissue in an athymic rat model. Tissue Eng 11:469–478
Hata H, Matsumiya G, Miyagawa S, Kondoh H, Kawaguchi N, Matsuura N, Shimizu T, Okano T, Matsuda H, Sawa Y (2006) Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing-induced canine heart failure model. J Thorac Cardiovasc Surg 132:918–924
Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B, Ganser A, Knapp WH, Drexler H (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111:2198–2202
Kanzaki M, Yamato M, Yang J, Sekine H, Kohno C, Takagi R, Hatakeyama H, Isaka T, Okano T, Onuki T (2007) Dynamic sealing of lung air leaks by the transplantation of tissue engineered cell sheets. Biomaterials 28:4294–4302
Kofidis T, de Bruin JL, Hoyt G, Lebl DR, Tanaka M, Yamane T, Chang CP, Robbins RC (2004) Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. J Thorac Cardiovasc Surg 128:571–578
Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, Takaku F, Yazaki Y (1990) Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem 265:3595–3598
Kondoh H, Sawa Y, Miyagawa S, Sakakida-Kitagawa S, Memon IA, Kawaguchi N, Matsuura N, Shimizu T, Okano T, Matsuda H (2006) Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters. Cardiovasc Res 69:466–475
Kubo H, Shimizu T, Yamato M, Fujimoto T, Okano T (2007) Creation of myocardial tubes using cardiomyocyte sheets and an in vitro cell sheet-wrapping device. Biomaterials 28:3508–3516
Kushida A, Yamato M, Konno C, Kikuchi A, Sakurai Y, Okano T (1999) Decrease in culture temperature releases monolayer endothelial cell sheets together with deposited fibronectin matrix from temperature-responsive culture surfaces. J Biomed Mater Res 45:355–362
Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856
Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926
Lee EJ, Kim do E, Azeloglu EU, Costa KD (2008) Engineered cardiac organoid chambers: Toward a functional biological model ventricle. Tissue Eng Part A 14:215–225
Leor J, Aboulafia-Etzion S, Dar A, Shapiro L, Barbash IM, Battler A, Granot Y, Cohen S (2000) Bioengineered cardiac grafts: A new approach to repair the infarcted myocardium? Circulation 102:III56–III61
Li RK, Jia ZQ, Weisel RD, Mickle DA, Choi A, Yau TM (1999) Survival and function of bioengineered cardiac grafts. Circulation 100:II63–II69
Memon IA, Sawa Y, Fukushima N, Matsumiya G, Miyagawa S, Taketani S, Sakakida SK, Kondoh H, Aleshin AN, Shimizu T, Okano T, Matsuda H (2005) Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. J Thorac Cardiovasc Surg 130:1333–1341
Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin JT, Marolleau JP (2001) Myoblast transplantation for heart failure. Lancet 357:279–280
Miyagawa S, Sawa Y, Sakakida S, Taketani S, Kondoh H, Memon IA, Imanishi Y, Shimizu T, Okano T, Matsuda H (2005) Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium. Transplantation 80:1586–1595
Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, Ishino K, Ishida H, Shimizu T, Kangawa K, Sano S, Okano T, Kitamura S, Mori H (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12:459–465
Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, Tano Y (2004) Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med 351:1187–1196
Ohki T, Yamato M, Murakami D, Takagi R, Yang J, Namiki H, Okano T, Takasaki K (2006) Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model. Gut 55:1704–1710
Okano T, Yamada N, Sakai H, Sakurai Y (1993) A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(n-isopropylacrylamide). J Biomed Mater Res 27:1243–1251
Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705
Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA (2008) Perfusion-decellularized matrix: Using nature's platform to engineer a bioartificial heart. Nat Med 14:213–221
Schluter KD, Piper HM (1999) Regulation of growth in the adult cardiomyocytes. FASEB J 13(Suppl):S17–S22
Sekine H, Shimizu T, Kosaka S, Kobayashi E, Okano T (2006) Cardiomyocyte bridging between hearts and bio-engineered myocardial tissues with mesenchymal transition of mesothelial cells. J Heart Lung Transplant 25(3):324–332
Sekine H, Shimizu T, Yang J, Kobayashi E, Okano T (2006) Pulsatile myocardial tubes fabricated with cell sheet engineering. Circulation 114:I87–I93
Sekine H, Shimizu T, Hobo K, Sekiya S, Yang J, Yamato M, Kurosawa H, Kobayashi E, Okano T (2008) Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances neovascularization and improves cardiac function of ischemic hearts. Circulation 118:S145–S152
Sekiya S, Shimizu T, Yamato M, Kikuchi A, Okano T (2006) Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential. Biochem Biophys Res Commun 341:573–582
Shimizu T, Yamato M, Kikuchi A, Okano T (2001) Two-dimensional manipulation of cardiac myocyte sheets utilizing temperature-responsive culture dishes augments the pulsatile amplitude. Tissue Eng 7:141–151
Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, Kikuchi A, Umezu M, Okano T (2002) Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res 90:e40
Shimizu T, Yamato M, Kikuchi A, Okano T (2003) Cell sheet engineering for myocardial tissue reconstruction. Biomaterials 24:2309–2316
Shimizu T, Sekine H, Isoi Y, Yamato M, Kikuchi A, Okano T (2006a) Long-term survival and growth of pulsatile myocardial tissue grafts engineered by the layering of cardiomyocyte sheets. Tissue Eng 12:499–507
Shimizu T, Sekine H, Yang J, Isoi Y, Yamato M, Kikuchi A, Kobayashi E, Okano T (2006b) Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick, vascularized myocardial tissues. FASEB J 20:708–710
Wollert KC (2008) Cell therapy for acute myocardial infarction. Curr Opin Pharmacol 8:202–210
Yamada N, Okano T, Sakai H, Karikusa F, Sawasaki Y, Sakurai Y (1990) Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells. Die Makromolekulare Chemie, Rapid Commun 11:571–576
Yang J, Yamato M, Shimizu T, Sekine H, Ohashi K, Kanzaki M, Ohki T, Nishida K, Okano T (2007) Reconstruction of functional tissues with cell sheet engineering. Biomaterials 28:5033–5043
Yildirim Y, Naito H, Didie M, Karikkineth BC, Biermann D, Eschenhagen T, Zimmermann WH (2007) Development of a biological ventricular assist device: Preliminary data from a small animal model. Circulation 116:I16–I23
Yost MJ, Baicu CF, Stonerock CE, Goodwin RL, Price RL, Davis JM, Evans H, Watson PD, Gore CM, Sweet J, Creech L, Zile MR, Terracio L (2004) A novel tubular scaffold for cardiovascular tissue engineering. Tissue Eng 10:273–284
Zandonella C (2003) Tissue engineering: The beat goes on. Nature 421:884–886
Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE (2001) Cardiomyocyte grafting for cardiac repair: Graft cell death and anti-death strategies. J Mol Cell Cardiol 33:907–921
Zimmermann WH, Didie M, Doker S, Melnychenko I, Naito H, Rogge C, Tiburcy M, Eschenhagen T (2006a) Heart muscle engineering: An update on cardiac muscle replacement therapy. Cardiovasc Res 71:419–429
Zimmermann WH, Melnychenko I, Wasmeier G, Didie M, Naito H, Nixdorff U, Hess A, Budinsky L, Brune K, Michaelis B, Dhein S, Schwoerer A, Ehmke H, Eschenhagen T (2006b) Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 12:452–458
Acknowledgements
The present work was supported in part by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” initiated by the Council for Science and Technology Policy (CSTP), the High-Tech Research (HRC) Program, and the Formation of Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science and Technology “Cell Sheet Tissue Engineering Center (CSTEC)” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sekine, H., Shimizu, T. & Okano, T. Myocardial tissue engineering: toward a bioartificial pump. Cell Tissue Res 347, 775–782 (2012). https://doi.org/10.1007/s00441-011-1267-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-011-1267-6