Effect of Rat Heart Tissue-derived Extracellular Matrix on Differentiation, Proliferation, and Apoptosis of Cardiosphere-derived Cells in Vitro_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

JIANGDa-qing ¹ ,  GUTian-xiang ¹ , XUZhao-fa ² , ZHANGGuang-wei ¹ , MAONai-hui ¹

1. Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang 110001, P. R. China;
2. Department of Environmental Health, Public Health College of China Medical University, Shenyang 110001, P. R. China;

Corresponding?author：

GUTian-xiang, Email: cmugtx@sina.com

Keywords：

Cardiosphere-drived cells; Heart tissue-derived extracellular matrix; Differentiation; Proliferation and apoptosis

DOI：

10.7507/1007-4848.20160216

Video：

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Objective To investigate effect of heart tissue-derived extracellular matrix(ECM) on the differentiation, proliferation and apoptosis of cardiosphere-derived cells(CDC) in vitro. Methods CDCs were cultured by cardiac explant methods. ECM was prepared by decelluariztion procedure. CDCs were cultured on ECM coated dishes or conventional fibrin (FN) coated dishes. Then we compared the differentiation rate, proliferation, and apoptosis rate of CDC between the two groups in vitro. Results ECM could significantly promote CDC differentiating into vascular endothelial cell, cardiac muscle cell or smooth muscle cell (0.060±0.002 vs. 0.043±0.002, P < 0.001; 0.082±0.003 vs. 0.051±0.002, P < 0.001; 0.055±0.002 vs. 0.034±0.001, P < 0.001). ECM also significantly promoted the proliferation of CDC and reduced the apoptosis and necrosis rate of CDC in vitro (0.052±0.002 vs. 0.025±0.001, P < 0.001). Conclusion We obtained c-kit⁺ CDCs, effectively remove the cellular components of heart tissue-derived ECM and preserved the composition and structure of ECM. ECM can promote the differentiation of CDC to vascular endothelial cell, cardiac muscle cell or smooth muscle cell, promote the proliferation of CDCs and decrease CDC apoptosis and necrosis rate in vitro.

Citation： JIANGDa-qing, GUTian-xiang, XUZhao-fa, ZHANGGuang-wei, MAONai-hui. Effect of Rat Heart Tissue-derived Extracellular Matrix on Differentiation, Proliferation, and Apoptosis of Cardiosphere-derived Cells in Vitro. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(9): 901-906. doi: 10.7507/1007-4848.20160216 Copy

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2.	Chimenti I, Smith RR, Li TS, et al. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res, 2010, 106(5):971-980.
3.	Gaetani R, Rizzitelli G, Chimenti I, et al. Cardiospheres and tissue engineering for myocardial regeneration:potential for clinical application. J Cell Mol Med, 2010, 14(5):1071-1077.
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11.	Tsur-Gang O, Ruvinov E, Landa N, et al. The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction. Biomaterials, 2009, 30(2):189-195.
12.	Zhao ZQ, Puskas JD, Xu D, et al. Improvement in cardiac function with small intestine extracellular matrix is associated with recruitment of c-kit cells, myofibroblasts, and macrophages after myocardial infarction. J Am Coll Cardiol, 2010, 55(12):1250-1261.
13.	Seif-Naraghi SB, Salvatore MA, Schup-Magoffin PJ, et al. Design and characterization of an injectable pericardial matrix gel:a potentially autologous scaffold for cardiac tissue engineering. Tissue Eng Part A, 2010, 16(6):2017-2027.
14.	Lin YD, Yeh ML, Yang YJ, et al. Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. Circulation, 2010, 122 (suppl 11):S132-S141.
15.	Cheng K, Malliaras K, Shen D, et al. Intramyocardial injection of platelet gel promotes endogenous repair and augments cardiac function in rats with myocardial infarction. J Am Coll Cardiol, 2012, 59(3):256-264.
16.	Singelyn JM, Sundaramurthy P, Johnson TD, et al. Catheter deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction. J Am Coll Cardiol, 2012, 59(8):751-763.
17.	Dai W, Hale SL, Kay GL, et al. Delivering stem cells to the heart in a collagen matrix reduces relocation of cells to other organs as assessed by nanoparticle technology. Regen Med, 2009, 4(3):387-395.
18.	Rufaihah AJ, Vaibavi SR, Plotkin M, et al. Enhanced infarct stabilization and neovascularization mediated by VEGF-loaded PEGylated fibrinogen hydrogel in a rodent myocardial infarction model. Biomaterials, 2013, 34(33):8195-8202.
19.	Davis ME, Motion JP, Narmoneva DA, et al. Injectable selfassembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation, 2005, 111(4):442-450.
20.	Huang NF, Yu J, Sievers R, et al. Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng, 2005, 11(11-12):1860-1866.
21.	Dai W, Kay GL, Jyrala AJ, et al. Experience from experimental cell transplantation therapy of myocardial infarction:what have we learned? Cell Transplant, 2013, 22(3):563-568.
22.	Zhang Y, He Y, Bharadwaj S, et al. Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotypes. Biomaterials, 2009, 30(23-24):4021-4028.
23.	Liu Y, Bharadwaj S, Lee SJ, et al. Optimization of a natural collagen scaffold to aid cell-matrix penetration for urologic tissue engineering. Biomaterials, 2009, 30(23-24):3865-3873.
24.	Lang R, Stern M, Leona SL, et al. 3D liver ECM for human hepatocyte growth and differenti-ation. Biomaterials, 2011, 32(29):7042-7052.
25.	Skardal A, Smith L, Bharadwaj S, et al. Tissue specific synthetic ECM hydrogels for in vitro maintenance of hepatocyte function. Biomaterials, 2012, 33(18):4565-4575.

1. Messina E, De Angelis L, Frati G. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res, 2004, 95(9):911-921.
2. Chimenti I, Smith RR, Li TS, et al. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res, 2010, 106(5):971-980.
3. Gaetani R, Rizzitelli G, Chimenti I, et al. Cardiospheres and tissue engineering for myocardial regeneration:potential for clinical application. J Cell Mol Med, 2010, 14(5):1071-1077.
4. Smith RR, Barile L, Cho HC, et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation, 2007, 115(7):896-908.
5. Gaetani R, Ledda M, Barile L, et al. Differentiation of human adult cardiac stem cells exposed to extremely low-frequency electromagnetic fields. Cardiovasc Res, 2009, 82(3):411-420.
6. Mishra R, Vijayan K, Colletti E, et al. Characterization and functionality of cardiac progenitor cells in congenital heart patients. Circulation, 2011, 123(4):364-373.
7. Dai WD, Gerczuk P, Zhang YY, et al. Intramyocardial injection of heart tissue-derived extracellular matrix improves postinfarction cardiac function in rats. J Cardiovasc Pharmacol Therap, 2013, 18(3):270-279.
8. Tous E, Ifkovits JL, Koomalsingh KJ, et al. Influence of injectable hyaluronic acid hydrogel degradation behavior on infarction induced ventricular remodeling. Bio Macromolecules, 2011, 12(11):4127-4135.
9. Christman KL, Fok HH, Sievers RE, et al. Fibrin glue alone and skeletal myoblasts in a fibrin scaffold preserve cardiac function after myocardial infarction. Tissue Eng, 2004, 10(3-4):403-409.
10. Dai W, Wold LE, Dow JS, et al. 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, 2005, 46(4):714-719.
11. Tsur-Gang O, Ruvinov E, Landa N, et al. The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction. Biomaterials, 2009, 30(2):189-195.
12. Zhao ZQ, Puskas JD, Xu D, et al. Improvement in cardiac function with small intestine extracellular matrix is associated with recruitment of c-kit cells, myofibroblasts, and macrophages after myocardial infarction. J Am Coll Cardiol, 2010, 55(12):1250-1261.
13. Seif-Naraghi SB, Salvatore MA, Schup-Magoffin PJ, et al. Design and characterization of an injectable pericardial matrix gel:a potentially autologous scaffold for cardiac tissue engineering. Tissue Eng Part A, 2010, 16(6):2017-2027.
14. Lin YD, Yeh ML, Yang YJ, et al. Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. Circulation, 2010, 122 (suppl 11):S132-S141.
15. Cheng K, Malliaras K, Shen D, et al. Intramyocardial injection of platelet gel promotes endogenous repair and augments cardiac function in rats with myocardial infarction. J Am Coll Cardiol, 2012, 59(3):256-264.
16. Singelyn JM, Sundaramurthy P, Johnson TD, et al. Catheter deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction. J Am Coll Cardiol, 2012, 59(8):751-763.
17. Dai W, Hale SL, Kay GL, et al. Delivering stem cells to the heart in a collagen matrix reduces relocation of cells to other organs as assessed by nanoparticle technology. Regen Med, 2009, 4(3):387-395.
18. Rufaihah AJ, Vaibavi SR, Plotkin M, et al. Enhanced infarct stabilization and neovascularization mediated by VEGF-loaded PEGylated fibrinogen hydrogel in a rodent myocardial infarction model. Biomaterials, 2013, 34(33):8195-8202.
19. Davis ME, Motion JP, Narmoneva DA, et al. Injectable selfassembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation, 2005, 111(4):442-450.
20. Huang NF, Yu J, Sievers R, et al. Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng, 2005, 11(11-12):1860-1866.
21. Dai W, Kay GL, Jyrala AJ, et al. Experience from experimental cell transplantation therapy of myocardial infarction:what have we learned? Cell Transplant, 2013, 22(3):563-568.
22. Zhang Y, He Y, Bharadwaj S, et al. Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotypes. Biomaterials, 2009, 30(23-24):4021-4028.
23. Liu Y, Bharadwaj S, Lee SJ, et al. Optimization of a natural collagen scaffold to aid cell-matrix penetration for urologic tissue engineering. Biomaterials, 2009, 30(23-24):3865-3873.
24. Lang R, Stern M, Leona SL, et al. 3D liver ECM for human hepatocyte growth and differenti-ation. Biomaterials, 2011, 32(29):7042-7052.
25. Skardal A, Smith L, Bharadwaj S, et al. Tissue specific synthetic ECM hydrogels for in vitro maintenance of hepatocyte function. Biomaterials, 2012, 33(18):4565-4575.

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