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Myocardial tissue engineering: toward a bioartificial pump

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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.

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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

    Article  PubMed  Google Scholar 

  • Christman KL, Lee RJ (2006) Biomaterials for the treatment of myocardial infarction. J Am Coll Cardiol 48:907–913

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856

    Article  PubMed  CAS  Google Scholar 

  • Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Li RK, Jia ZQ, Weisel RD, Mickle DA, Choi A, Yau TM (1999) Survival and function of bioengineered cardiac grafts. Circulation 100:II63–II69

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Schluter KD, Piper HM (1999) Regulation of growth in the adult cardiomyocytes. FASEB J 13(Suppl):S17–S22

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Sekine H, Shimizu T, Yang J, Kobayashi E, Okano T (2006) Pulsatile myocardial tubes fabricated with cell sheet engineering. Circulation 114:I87–I93

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Shimizu T, Yamato M, Kikuchi A, Okano T (2003) Cell sheet engineering for myocardial tissue reconstruction. Biomaterials 24:2309–2316

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Wollert KC (2008) Cell therapy for acute myocardial infarction. Curr Opin Pharmacol 8:202–210

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Zandonella C (2003) Tissue engineering: The beat goes on. Nature 421:884–886

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

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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.

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Correspondence to Teruo Okano.

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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

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  • DOI: https://doi.org/10.1007/s00441-011-1267-6

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