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Tissue Engineering for Myocardial Regeneration

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Stem Cell Therapy and Tissue Engineering for Cardiovascular Repair

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8. Conclusions

In this chapter, we describe an in vitro method for the formation of contractile 3-D cardiac muscle, which we have termed cardioids. Cardioids are formed from the spontaneous delamination of a confluent monolayer of primary cardiac myocytes. One of the most attractive features of the cardioid model is that isolated cardiac cells self-organize to form 3-D cardiac muscle. This eliminates the need for synthetic scaffolding material in the contractile region of cardioids and allows cardioids to exhibit uninhibited contractions. Cardioids have been shown to exhibit several physiologically relevant metrics of function. Cardioids can be electrically stimulated to generate active force and can be electrically paced at frequencies of 1–7 Hz. In addition, cardioids are responsive to calcium and various cardio-active drugs. The cardioid model has several potential applications in basic research and may provide viable cardiac tissue for clinical applications.

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10. References

  1. 2002 Heart and Stroke Statistical Update, American Heart Association. 2002.

    Google Scholar 

  2. Miniati DN, Robbins RC. Heart transplantation: a thirty-year perspective. [Review] [74 refs]. Annual Review of Medicine. 2002;53:189–205.

    Article  Google Scholar 

  3. Goldstein S. Heart failure therapy at the turn of the century. [Review] [53 refs]. Heart Failure Reviews. 2001;6:7–14.

    MATH  Google Scholar 

  4. Stevenson LW, Kormos RL. Mechanical cardiac support 2000: current applications and future trial design. [Review] [111 refs]. Journal of Heart & Lung Transplantation. 2001;20:1–38.

    Google Scholar 

  5. Stevenson LW, Warner SL, Steimle AE, Fonarow GC, Hamilton MA, Moriguchi JD, Kobashigawa JA, Tillisch JH, Drinkwater DC, Laks H. The impending crisis awaiting cardiac transplantation. Modeling a solution based on selection. Circulation 89(1):450–7. 1994.

    Google Scholar 

  6. Eschenhagen T, Fink C, Remmers U, Scholz H, Wattchow J, Weil J, Zimmermann W, Dohmen HH, Schafer H, Bishopric N, Wakatsuki T, Elson EL. Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. FASEB Journal. 1997;11:683–694.

    Google Scholar 

  7. Akins RE. Can tissue engineering mend broken hearts? [letter; comment.]. Circulation Research. 2002;90:120–122.

    Google Scholar 

  8. Eschenhagen T, Didie M, Heubach J, Ravens U, Zimmermann WH. Cardiac tissue engineering. [Review] [21 refs]. Transplant Immunology. 2002;9:315–321.

    Article  Google Scholar 

  9. Papadaki M. Cardiac muscle tissue engineering. [Review] [13 refs]. IEEE Engineering in Medicine & Biology Magazine. 2003;22:153–154.

    Google Scholar 

  10. Shimizu T, Yamato M, Kikuchi A, Okano T. Cell sheet engineering for myocardial tissue reconstruction. [Review] [38 refs]. Biomaterials. 2003;24:2309–2316.

    Article  Google Scholar 

  11. Zimmermann WH, Eschenhagen T. Cardiac tissue engineering for replacement therapy. [Review] [79 refs]. Heart Failure Reviews. 2003;8:259–269.

    Article  Google Scholar 

  12. Fedak PW, Weisel RD, Verma S, Mickle DA, Li RK. Restoration and regeneration of failing myocardium with cell transplantation and tissue engineering. [Review] [78 refs]. Seminars in Thoracic & Cardiovascular Surgery. 2003;15:277–286.

    Google Scholar 

  13. Carrier RL, Papadaki M, Rupnick M, Schoen FJ, Bursac N, Langer R, Freed LE, Vunjak-Novakovic G. Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization. Biotechnology & Bioengineering. 1999;64:580–589.

    Article  Google Scholar 

  14. Bursac N, Papadaki M, Cohen RJ, Schoen FJ, Eisenberg SR, Carrier R, Vunjak-Novakovic G, Freed LE. Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies. American Journal of Physiology. 1999;277:t-44.

    Google Scholar 

  15. Papadaki M, Bursac N, Langer R, Merok J, Vunjak-Novakovic G, Freed LE. Tissue engineering of functional cardiac muscle: molecular, structural, and electrophysiological studies. American Journal of Physiology-Heart & Circulatory Physiology. 2001;280:H168–H178.

    Google Scholar 

  16. Carrier RL, Rupnick M, Langer R, Schoen FJ, Freed LE, Vunjak-Novakovic G. Perfusion improves tissue architecture of engineered cardiac muscle. Tissue Engineering. 2002;8:175–188.

    Article  Google Scholar 

  17. Carrier RL, Rupnick M, Langer R, Schoen FJ, Freed LE, Vunjak-Novakovic G. Effects of oxygen on engineered cardiac muscle. Biotechnology & Bioengineering. 2002;78:617–625.

    Article  Google Scholar 

  18. Zimmermann WH, Fink C, Kralisch D, Remmers U, Weil J, Eschenhagen T. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnology & Bioengineering. 2000;68:106–114.

    Article  Google Scholar 

  19. Zimmermann WH, Schneiderbanger K, Schubert P, Didie M, Munzel F, Heubach JF, Kostin S, Neuhuber WL, Eschenhagen T. Tissue engineering of a differentiated cardiac muscle construct. [see comments.]. Circulation Research. 2002;90:223–230.

    Article  Google Scholar 

  20. Zimmermann WH, Didie M, Wasmeier GH, Nixdorff U, Hess A, Melnychenko I, Boy O, Neuhuber WL, Weyand M, Eschenhagen T. Cardiac grafting of engineered heart tissue in syngenic rats. Circulation. 2002;106:Suppl-7.

    Google Scholar 

  21. Eschenhagen T, Didie M, Munzel F, Schubert P, Schneiderbanger K, Zimmermann WH. 3D engineered heart tissue for replacement therapy. Basic Research in Cardiology. 2002;97:Suppl-52.

    Google Scholar 

  22. Fink C, Ergun S, Kralisch D, Remmers U, Weil J, Eschenhagen T. Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement. FASEB Journal. 2000;14:669–679.

    Google Scholar 

  23. Okano T, Yamada N, Sakai H, Sakurai Y. A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide). Journal of Biomedical Materials Research. 1993;27:1243–1251.

    Google Scholar 

  24. Shimizu T, Yamato M, Kikuchi A, Okano T. Two-dimensional manipulation of cardiac myocyte sheets utilizing temperature-responsive culture dishes augments the pulsatile amplitude. Tissue Engineering. 2001;7:141–151.

    Article  Google Scholar 

  25. Okano T, Yamada N, Okuhara M, Sakai H, Sakurai Y. Mechanism of cell detachment from temperature-modulated, hydrophilic-hydrophobic polymer surfaces. Biomaterials. 1995;16:297–303.

    Article  Google Scholar 

  26. Shimizu T, Yamato M, Akutsu T, Shibata T, Isoi Y, Kikuchi A, Umezu M, Okano T. Electrically communicating three-dimensional cardiac tissue mimic fabricated by layered cultured cardiomyocyte sheets. Journal of Biomedical Materials Research. 2002;60:110–117.

    Article  Google Scholar 

  27. Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, Kikuchi A, Umezu M, Okano T. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circulation Research. 2002;90:e40.

    Article  Google Scholar 

  28. Akins RE, Boyce RA, Madonna ML, Schroedl NA, Gonda SR, McLaughlin TA, Hartzell CR. Cardiac organogenesis in vitro: reestablishment of three-dimensional tissue architecture by dissociated neonatal rat ventricular cells. Tissue Engineering. 1999;5:103–118.

    Google Scholar 

  29. Li RK, Yau TM, Weisel RD, Mickle DA, Sakai T, Choi A, Jia ZQ. Construction of a bioengineered cardiac graft. Journal of Thoracic & Cardiovascular Surgery. 2000;119:368–375.

    Google Scholar 

  30. Ozawa T, Mickle DA, Weisel RD, Koyama N, Wong H, Ozawa S, Li RK. Histologic changes of nonbiodegradable and biodegradable biomaterials used to repair right ventricular heart defects in rats. Journal of Thoracic & Cardiovascular Surgery 124(6):1157–64. 2002.

    Google Scholar 

  31. Ozawa T, Mickle DA, Weisel RD, Koyama N, Ozawa S, Li RK. Optimal biomaterial for creation of autologous cardiac grafts. Circulation. 2002;106:Suppl-82.

    Google Scholar 

  32. Li RK, Jia ZQ, Weisel RD, Mickle DA, Choi A, Yau TM. Survival and function of bioengineered cardiac grafts. Circulation. 1999;100:Suppl-9.

    Google Scholar 

  33. Sakai T, Li RK, Weisel RD, Mickle DA, Kim ET, Jia ZQ, Yau TM. The fate of a tissue-engineered cardiac graft in the right ventricular outflow tract of the rat. Journal of Thoracic & Cardiovascular Surgery. 2001;121:932–942.

    Google Scholar 

  34. Akhyari P, Fedak PW, Weisel RD, Lee TY, Verma S, Mickle DA, Li RK. Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts. Circulation. 2002;106:Suppl-42.

    Google Scholar 

  35. Leor J, Aboulafia-Etzion S, Dar A, Shapiro L, Barbash IM, Battler A, Granot Y, Cohen S. Bioengineered cardiac grafts: A new approach to repair the infracted myocardium? Circulation. 2000;102:Suppl-61.

    Google Scholar 

  36. Dar A, Shachar M, Leor J, Cohen S. Optimization of cardiac cell seeding and distribution in 3D porous alginate scaffolds. Biotechnology & Bioengineering. 2002;80:305–312.

    Article  Google Scholar 

  37. Baar K, Birla R, Boluyt MO, Borschel GH, Arruda EM, Dennis RG. Heart muscle by design: Self-organization of ratcardiac cells into contractile 3-D cardiac tissue. FASEB Journal. 4 A.D..

    Google Scholar 

  38. Dennis RG, Kosnik PE. Excitability and isometric contractile properties of mammalian skeletal muscle constructs engineered in vitro. In Vitro Cellular & Developmental Biology Animal. 2000;36:327–335.

    Google Scholar 

  39. Dennis RG, Kosnik PE, Gilbert ME, Faulkner JA. Excitability and contractility of skeletal muscle engineered from primary cultures and cell lines. American Journal of Physiology-Cell Physiology. 2001;280:C288–C295.

    Google Scholar 

  40. Kosnik PE, Faulkner JA, Dennis RG. Functional development of engineered skeletal muscle from adult and neonatal rats. Tissue Engineering. 2001;7:573–584.

    Article  Google Scholar 

  41. Kosnik PE, Dennis RG. Mesenchymal Cell Culture: Functional Mammalian Skeletal Muscle Constructs. In: Methods of Tissue Engineering. Anthony Atala RPL, ed. 2002. Academic Press.

    Google Scholar 

  42. Dennis RG, Kosnik PE. Mesenchymal Cell Culture: Instrumentation and Methods for Evaluating Engineered Muscle. In: Methods of Tissue Engineering. Anthony Atala RPL, ed. 2002. Academic Press.

    Google Scholar 

  43. Layland J, Young IS, Altringham JD. The effect of cycle frequency on the power output of rat papillary muscles in vitro. Journal of Experimental Biology. 198;1035–1043.

    Google Scholar 

  44. Friedman WF. The intrinsic physiologic properties of the developing heart. Progress in Cardiovascular Diseases 15(1):87–111. 1972;-Aug.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Section of Cardiac Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, 48109-2007

    Ravi K. Birla

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  1. Ravi K. Birla
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Editors and Affiliations

  1. Arizona Heart Institute, 2632 North 20th Street, Phoenix, AZ, 85006, USA

    Nabil Dib MD, MSc, FACC (Director of Cardiovascular Research) & Edward B. Diethrich MD (Medical Director) (Director of Cardiovascular Research) &  (Medical Director)

  2. Center for Cardiovascular Repair, University of Minnesota, Minneapolis, MN, USA

    Doris A. Taylor PhD (Director) (Director)

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Birla, R.K. (2006). Tissue Engineering for Myocardial Regeneration. In: Dib, N., Taylor, D.A., Diethrich, E.B. (eds) Stem Cell Therapy and Tissue Engineering for Cardiovascular Repair. Springer, Boston, MA. https://doi.org/10.1007/0-387-30939-X_16

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  • DOI: https://doi.org/10.1007/0-387-30939-X_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-25788-4

  • Online ISBN: 978-0-387-30939-2

  • eBook Packages: EngineeringEngineering (R0)

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