Engineered Heart Tissues——How Long to Go from Bench to Clinic_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHENKe-gong , XIEBao-dong ,  KANGKai , JIANGShu-lin

Department of Cardiovascular Surgery, 2 nd Affiliated Hospital of Harbin Medical University, Key Laboratory of Myocardial Ischemia Mechanism and Treatment, Ministry of Education, Harbin 150086, P. R. China;

Corresponding author：

KANGKai, Email: kangkai1975@sina.com

Keywords：

Engineered heart tissue; Seeding cells; Scaffold; Vascularization

DOI：

10.7507/1007-4848.20150149

Video：

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The engineered heart tissues (EHTs) present a promising alternative to current materials for native myocardial tissue due to the unique characteristics. However, until now, the clinical application of EHTs is limited by a serial of practical problems yet. Generally, the challenges need to further optimize include biomaterials, cell sources, and strategies of revascularization or establishment of EHTs. This review focuses on the newly progress on these aspects to encourage the emergence of novel EHTs that can meet clinic requirement properly.

Citation： CHENKe-gong, XIEBao-dong, KANGKai, JIANGShu-lin. Engineered Heart Tissues——How Long to Go from Bench to Clinic. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(6): 591-595. doi: 10.7507/1007-4848.20150149 Copy

1.	Li RK, Jia ZQ, Weisel RD, et al. Survival and function of bioengin-eered cardiac grafts. Circulation, 1999, 100(19 Suppl): Ⅱ63-Ⅱ69.
2.	Leor J, Aboulafia-Etzion S, Dar A, et al. Bioengineered cardiac grafts: A new approach to repair the infarcted myocardium? Circulation, 2000, 102 (19 Suppl 3): ⅡI56-Ⅱ61.
3.	Chiu RC, Zibaitis A, Kao RL.Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg, 1995, 60 (1): 12-18.
4.	Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med, 1998, 4(8): 929-933.
5.	Abraham MR, Henrikson CA, Tung L, et al. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ Res, 2005, 97(2): 159-167.
6.	Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol, 2003, 42(12): 2063-2069.
7.	Siminiak T, Kalawski R, Fiszer D, et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J, 2004, 148(3): 531-537.
8.	Puceat M. Embryological origin of the endocardium and derived valve progenitor cells: from developmental biology to stem cell-based valve repair. Biochim Biophys Acta, 2013, 1833(4): 917-922.
9.	Yang L, Soonpaa MH, Adler ED, et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature, 2008, 453(7194): 524-528.
10.	Makino S, Fukuda K, Miyoshi S, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest, 1999, 103(5): 697-705.
11.	Huang XP, Sun Z, Miyagi Y, et al. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation, 2010, 122(23): 2419-2429.
12.	Rangappa S, Fen C, Lee EH, et al. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg, 2003, 75(3): 775-779.
13.	Perin EC, Willerson JT.Buying new soul. J Am Coll Cardiol, 2012, 60(21): 2250-2251.
14.	Bayes-Genis A, Soler-Botija C, Farre J. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. J Mol Cell Cardiol, 2010, 49(5): 771-780.
15.	Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med, 2003, 9(9): 1195-1201.
16.	Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 2003, 114(6): 763-776.
17.	Ellison GM, Torella D, Karakikes I, et al. Myocyte death and renewal: modern concepts of cardiac cellular homeostasis. Nat Clin Pract Cardiovasc Med, 2007, 4(Suppl 1): S52-S59.
18.	Padin-Iruegas ME, Misao Y, Davis ME, et al. Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. Circulation, 2009, 120(10): 876-887.
19.	Tulloch NL, Muskheli V, Razumova MV, et al. Growth of engine-ered human myocardium with mechanical loading and vascular coculture. Circ Res, 2011, 109(1): 47-59.
20.	Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Ther, 2005, 105(2): 151-163.
21.	Tee R, Lokmic Z, Morrison WA.Strategies in cardiac tissue enginee-ring. ANZ J Surg, 2010, 80(10): 683-693.
22.	Matsuura K, Honda A, Nagai T, et al. Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. J Clin Invest, 2009, 119(8): 2204-2217.
23.	Bel A, Planat-Bernard V, Saito A, et al. Composite cell sheets: a further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation, 2010, 122(11 Suppl): S118-123.
24.	Sawa Y. Myocardial regeneration for heart failure. Nihon Rinsho, 2010, 68: 719-725.
25.	Lu TY, Lin B, Kim J, et al. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovas-cular progenitor cells. Nat Commun, 2013, 4: 2307.
26.	Robertson MJ, Dries-Devlin JL, Kren SM, et al. Optimizing recellularization of whole decellularized heart extracellular matrix. PLoS One, 2014, 9(2): e90406.
27.	Wainwright JM, Czajka CA, Patel UB, et al. Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng Part C Methods, 2010, 16(3): 525-532.
28.	Taylor DA. From stem cells and cadaveric matrix to engineered organs. Curr Opin Biotechnol, 2009, 20 (5): 598-605.
29.	Korecky B, Hai CM, Rakusan K. Functional capillary density in normal and transplanted rat hearts. Can J Physiol Pharmacol, 1982, 60(1): 23-32.
30.	Radisic M, Malda J, Epping E, et al. Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol Bioeng, 2006, 93(2): 332-343.
31.	Iyer RK, Chiu LL, Radisic M. Microfabricated poly(ethylene glycol) templates enable rapid screening of triculture conditions for cardiac tissue engineering. J Biomed Mater Res A, 2009, 89(3): 616-631.
32.	Shimizu T, Yamato M, Isoi Y, et al. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res, 2002, 90(3): e40.
33.	Zhang C, Hou J, Zheng S, et al. Vascularized atrial tissue patch cardiomyoplasty with omentopexy improves cardiac performance after myocardial infarction. Ann Thorac Surg, 2011, 92(4): 1435-1442.
34.	Huang W, Zhang D, Millard RW, et al. Gene manipulated perito-neal cell patch repairs infarcted myocardium. J Mol Cell Cardiol, 2010, 48(4): 702-712.
35.	Morritt AN, Bortolotto SK, Dilley RJ, et al. Cardiac tissue enginee-ring in an in vivo vascularized chamber. Circulation, 2007, 115(3): 353-360.
36.	Steffens GC, Yao C, Prevel P, et al. Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor. Tissue Eng, 2004, 10(9-10): 1502-1509.
37.	Lee KY, Peters MC, Anderson KW, et al. Controlled growth factor release from synthetic extracellular matrices. Nature, 2000, 408(6815): 998-1000.
38.	Gao J, Liu J, Gao Y, et al. A myocardial patch made of collagen membranes loaded with collagen-binding human vascular endothelial growth factor accelerates healing of the injured rabbit heart. Tissue Eng Part A, 2011, 17(21-22): 2739-2747.
39.	Chiu LL, Radisic M. Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues. Biomaterials, 2010, 31(2): 226-241.
40.	Moscona AA. Tissues from dissociated cells. Sci Am, 1959, 200(5): 132-134.
41.	McDonald TF, Sachs HG, DeHaan RL.Development of sensitivity to tetrodotoxin in beating chick embryo hearts, single cells, and aggregates. Science, 1972, 176(4040): 1248-1250.
42.	Radisic M, Park H, Chen F, et al. Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds. Tissue Eng, 2006, 12(8): 2077-2091.
43.	Radisic M, Park H, Gerecht S, et al. Biomimetic approach to cardiac tissue engineering. Philos Trans R Soc Lond B Biol Sci, 2007, 362(1484): 1357-1368.
44.	Nunes SS, Miklas JW, Liu J, et al. Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods, 2013, 10(8): 781-787.
45.	Iyer RK, Chiu LL, Reis LA, et al. Engineered cardiac tissues. Curr Opin Biotechnol, 2011, 22(5): 706-714.
46.	Tandon N, Taubman A, Cimetta E, et al. Portable bioreactor for perfusion and electrical stimulation of engineered cardiac tissue. Conf Proc IEEE Eng Med Biol Soc, 2013: 6219-6223.
47.	Terracio L, Miller B, Borg TK. Effects of cyclic mechanical stimulation of the cellular components of the heart: in vitro. In Vitro Cell Dev Biol, 1988, 24(1): 53-58.
48.	Tranquillo RT, Girton TS, Bromberek BA, et al. Magnetically orientated tissue-equivalent tubes: application to a circumferentially orientated media-equivalent. Biomaterials, 1996, 17(3): 349-357.
49.	Thomas SP, Bircher-Lehmann L, Thomas SA, et al. Synthetic strands of neonatal mouse cardiac myocytes: structural and electrophysiological properties. Circ Res, 2000, 87(6): 467-473.
50.	Badrossamay MR, McIlwee HA, Goss JA, et al. Nanofiber assembly by rotary jet-spinning. Nano Lett, 2010, 10(6): 2257-2261.
51.	Kim DH, Lipke EA, Kim P, et al. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc Natl Acad Sci USA, 2010, 107(2): 565-570.
52.	Alford PW, Feinberg AW, Sheehy SP, et al. Biohybrid thin films for measuring contractility in engineered cardiovascular muscle. Biomaterials, 2010, 31(13): 3613-3621.
53.	Badie N, Bursac N. Novel micropatterned cardiac cell cultures with realistic ventricular microstructure. Biophys J, 2009, 96(9): 3873-3885.

1. Li RK, Jia ZQ, Weisel RD, et al. Survival and function of bioengin-eered cardiac grafts. Circulation, 1999, 100(19 Suppl): Ⅱ63-Ⅱ69.
2. Leor J, Aboulafia-Etzion S, Dar A, et al. Bioengineered cardiac grafts: A new approach to repair the infarcted myocardium? Circulation, 2000, 102 (19 Suppl 3): ⅡI56-Ⅱ61.
3. Chiu RC, Zibaitis A, Kao RL.Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg, 1995, 60 (1): 12-18.
4. Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med, 1998, 4(8): 929-933.
5. Abraham MR, Henrikson CA, Tung L, et al. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ Res, 2005, 97(2): 159-167.
6. Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol, 2003, 42(12): 2063-2069.
7. Siminiak T, Kalawski R, Fiszer D, et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J, 2004, 148(3): 531-537.
8. Puceat M. Embryological origin of the endocardium and derived valve progenitor cells: from developmental biology to stem cell-based valve repair. Biochim Biophys Acta, 2013, 1833(4): 917-922.
9. Yang L, Soonpaa MH, Adler ED, et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature, 2008, 453(7194): 524-528.
10. Makino S, Fukuda K, Miyoshi S, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest, 1999, 103(5): 697-705.
11. Huang XP, Sun Z, Miyagi Y, et al. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation, 2010, 122(23): 2419-2429.
12. Rangappa S, Fen C, Lee EH, et al. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg, 2003, 75(3): 775-779.
13. Perin EC, Willerson JT.Buying new soul. J Am Coll Cardiol, 2012, 60(21): 2250-2251.
14. Bayes-Genis A, Soler-Botija C, Farre J. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. J Mol Cell Cardiol, 2010, 49(5): 771-780.
15. Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med, 2003, 9(9): 1195-1201.
16. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 2003, 114(6): 763-776.
17. Ellison GM, Torella D, Karakikes I, et al. Myocyte death and renewal: modern concepts of cardiac cellular homeostasis. Nat Clin Pract Cardiovasc Med, 2007, 4(Suppl 1): S52-S59.
18. Padin-Iruegas ME, Misao Y, Davis ME, et al. Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. Circulation, 2009, 120(10): 876-887.
19. Tulloch NL, Muskheli V, Razumova MV, et al. Growth of engine-ered human myocardium with mechanical loading and vascular coculture. Circ Res, 2011, 109(1): 47-59.
20. Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Ther, 2005, 105(2): 151-163.
21. Tee R, Lokmic Z, Morrison WA.Strategies in cardiac tissue enginee-ring. ANZ J Surg, 2010, 80(10): 683-693.
22. Matsuura K, Honda A, Nagai T, et al. Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. J Clin Invest, 2009, 119(8): 2204-2217.
23. Bel A, Planat-Bernard V, Saito A, et al. Composite cell sheets: a further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation, 2010, 122(11 Suppl): S118-123.
24. Sawa Y. Myocardial regeneration for heart failure. Nihon Rinsho, 2010, 68: 719-725.
25. Lu TY, Lin B, Kim J, et al. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovas-cular progenitor cells. Nat Commun, 2013, 4: 2307.
26. Robertson MJ, Dries-Devlin JL, Kren SM, et al. Optimizing recellularization of whole decellularized heart extracellular matrix. PLoS One, 2014, 9(2): e90406.
27. Wainwright JM, Czajka CA, Patel UB, et al. Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng Part C Methods, 2010, 16(3): 525-532.
28. Taylor DA. From stem cells and cadaveric matrix to engineered organs. Curr Opin Biotechnol, 2009, 20 (5): 598-605.
29. Korecky B, Hai CM, Rakusan K. Functional capillary density in normal and transplanted rat hearts. Can J Physiol Pharmacol, 1982, 60(1): 23-32.
30. Radisic M, Malda J, Epping E, et al. Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol Bioeng, 2006, 93(2): 332-343.
31. Iyer RK, Chiu LL, Radisic M. Microfabricated poly(ethylene glycol) templates enable rapid screening of triculture conditions for cardiac tissue engineering. J Biomed Mater Res A, 2009, 89(3): 616-631.
32. Shimizu T, Yamato M, Isoi Y, et al. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res, 2002, 90(3): e40.
33. Zhang C, Hou J, Zheng S, et al. Vascularized atrial tissue patch cardiomyoplasty with omentopexy improves cardiac performance after myocardial infarction. Ann Thorac Surg, 2011, 92(4): 1435-1442.
34. Huang W, Zhang D, Millard RW, et al. Gene manipulated perito-neal cell patch repairs infarcted myocardium. J Mol Cell Cardiol, 2010, 48(4): 702-712.
35. Morritt AN, Bortolotto SK, Dilley RJ, et al. Cardiac tissue enginee-ring in an in vivo vascularized chamber. Circulation, 2007, 115(3): 353-360.
36. Steffens GC, Yao C, Prevel P, et al. Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor. Tissue Eng, 2004, 10(9-10): 1502-1509.
37. Lee KY, Peters MC, Anderson KW, et al. Controlled growth factor release from synthetic extracellular matrices. Nature, 2000, 408(6815): 998-1000.
38. Gao J, Liu J, Gao Y, et al. A myocardial patch made of collagen membranes loaded with collagen-binding human vascular endothelial growth factor accelerates healing of the injured rabbit heart. Tissue Eng Part A, 2011, 17(21-22): 2739-2747.
39. Chiu LL, Radisic M. Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues. Biomaterials, 2010, 31(2): 226-241.
40. Moscona AA. Tissues from dissociated cells. Sci Am, 1959, 200(5): 132-134.
41. McDonald TF, Sachs HG, DeHaan RL.Development of sensitivity to tetrodotoxin in beating chick embryo hearts, single cells, and aggregates. Science, 1972, 176(4040): 1248-1250.
42. Radisic M, Park H, Chen F, et al. Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds. Tissue Eng, 2006, 12(8): 2077-2091.
43. Radisic M, Park H, Gerecht S, et al. Biomimetic approach to cardiac tissue engineering. Philos Trans R Soc Lond B Biol Sci, 2007, 362(1484): 1357-1368.
44. Nunes SS, Miklas JW, Liu J, et al. Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods, 2013, 10(8): 781-787.
45. Iyer RK, Chiu LL, Reis LA, et al. Engineered cardiac tissues. Curr Opin Biotechnol, 2011, 22(5): 706-714.
46. Tandon N, Taubman A, Cimetta E, et al. Portable bioreactor for perfusion and electrical stimulation of engineered cardiac tissue. Conf Proc IEEE Eng Med Biol Soc, 2013: 6219-6223.
47. Terracio L, Miller B, Borg TK. Effects of cyclic mechanical stimulation of the cellular components of the heart: in vitro. In Vitro Cell Dev Biol, 1988, 24(1): 53-58.
48. Tranquillo RT, Girton TS, Bromberek BA, et al. Magnetically orientated tissue-equivalent tubes: application to a circumferentially orientated media-equivalent. Biomaterials, 1996, 17(3): 349-357.
49. Thomas SP, Bircher-Lehmann L, Thomas SA, et al. Synthetic strands of neonatal mouse cardiac myocytes: structural and electrophysiological properties. Circ Res, 2000, 87(6): 467-473.
50. Badrossamay MR, McIlwee HA, Goss JA, et al. Nanofiber assembly by rotary jet-spinning. Nano Lett, 2010, 10(6): 2257-2261.
51. Kim DH, Lipke EA, Kim P, et al. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc Natl Acad Sci USA, 2010, 107(2): 565-570.
52. Alford PW, Feinberg AW, Sheehy SP, et al. Biohybrid thin films for measuring contractility in engineered cardiovascular muscle. Biomaterials, 2010, 31(13): 3613-3621.
53. Badie N, Bursac N. Novel micropatterned cardiac cell cultures with realistic ventricular microstructure. Biophys J, 2009, 96(9): 3873-3885.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Engineered Heart Tissues——How Long to Go from Bench to Clinic

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