Bioengineered Myocardium Derived from Induced Pluripotent Stem Cells Improves Cardiac Function and Attenuates Cardiac Remodeling Following Chronic Myocardial Infarction in Rats

Overview

Journal Stem Cells Transl Med

Publisher Oxford University Press

Specialties Cell Biology
Pharmacology

Date 2012 Dec 1

PMID 23197822

Citations 44

Authors

Kenji Miki

Hisazumi Uenaka

Atsuhiro Saito

Shigeru Miyagawa

Taichi Sakaguchi

Takahiro Higuchi

Tatsuya Shimizu

Teruo Okano

Shinya Yamanaka

Yoshiki Sawa

Affiliations

Soon will be listed here.

Abstract

Cell-based therapies are promising strategies for myocardial repair following myocardial infarction. Induced pluripotent stem (iPS) cells have the potential to generate many cardiomyocytes, and they hold significant promise for the application of regenerative medicine to heart failure. Here, we developed cardiac tissue sheets, termed bioengineered myocardium (BM), from mouse iPS cells and measured cardiac performance following BM implantation in a rat chronic myocardial infarction model. Immunostaining analyses revealed that the α-actinin(+) cell population was isolated with more than 99% purity under specific culture conditions. To evaluate the contribution of BM to the improvements in cardiac performance, we induced myocardial infarction in 30 F344/NJcl-rnu/rnu rats by left anterior descending coronary ligation. The rats were randomly divided into two groups, 2 weeks after ligation: a BM implantation group (n = 15) and a sham group (n = 15). Echocardiography and catheter examination showed that the BM implantation significantly improved cardiac function and attenuated cardiac remodeling compared with the sham group. Histological analyses demonstrated that the implanted BM survived at the epicardial implantation site 4 weeks after implantation. The implanted BM survived and attenuated left ventricular remodeling in the rat chronic myocardial infarction model. Thus, BM derived from iPS cells might be a promising new treatment for heart failure.

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References

Miyagawa S, Sawa Y, Sakakida S, Taketani S, Kondoh H, Memon I . Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium. Transplantation. 2005; 80(11):1586-95. DOI: 10.1097/01.tp.0000181163.69108.dd. View

Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park I . Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation. 2009; 120(15):1513-23. DOI: 10.1161/CIRCULATIONAHA.109.868885. View

Bolli R, Chugh A, DAmario D, Loughran J, Stoddard M, Ikram S . Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011; 378(9806):1847-57. PMC: 3614010. DOI: 10.1016/S0140-6736(11)61590-0. View

Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T . Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2007; 26(1):101-6. DOI: 10.1038/nbt1374. View

Lloyd-Jones D, Adams R, Brown T, Carnethon M, Dai S, de Simone G . Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2009; 121(7):e46-e215. DOI: 10.1161/CIRCULATIONAHA.109.192667. View

Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K . 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. DOI: 10.1161/hh0302.105722. View

Li X, Yu X, Lin Q, Deng C, Shan Z, Yang M . Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment. J Mol Cell Cardiol. 2006; 42(2):295-303. DOI: 10.1016/j.yjmcc.2006.07.002. View

Yokoo N, Baba S, Kaichi S, Niwa A, Mima T, Doi H . The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells. Biochem Biophys Res Commun. 2009; 387(3):482-8. DOI: 10.1016/j.bbrc.2009.07.052. View

Reinecke H, Minami E, Zhu W, Laflamme M . Cardiogenic differentiation and transdifferentiation of progenitor cells. Circ Res. 2008; 103(10):1058-71. PMC: 2748983. DOI: 10.1161/CIRCRESAHA.108.180588. View

10.

Memon I, Sawa Y, Fukushima N, Matsumiya G, Miyagawa S, Taketani S . Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. J Thorac Cardiovasc Surg. 2005; 130(5):1333-41. DOI: 10.1016/j.jtcvs.2005.07.023. View

11.

Ebelt H, Jungblut M, Zhang Y, Kubin T, Kostin S, Technau A . Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines. Stem Cells. 2006; 25(1):236-44. DOI: 10.1634/stemcells.2006-0374. View

12.

Suzuki K, Murtuza B, Fukushima S, Smolenski R, Varela-Carver A, Coppen S . Targeted cell delivery into infarcted rat hearts by retrograde intracoronary infusion: distribution, dynamics, and influence on cardiac function. Circulation. 2004; 110(11 Suppl 1):II225-30. DOI: 10.1161/01.CIR.0000138191.11580.e3. View

13.

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K . Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131(5):861-72. DOI: 10.1016/j.cell.2007.11.019. View

14.

Uemura R, Xu M, Ahmad N, Ashraf M . Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006; 98(11):1414-21. DOI: 10.1161/01.RES.0000225952.61196.39. View

15.

Murry C, Field L, Menasche P . Cell-based cardiac repair: reflections at the 10-year point. Circulation. 2005; 112(20):3174-83. DOI: 10.1161/CIRCULATIONAHA.105.546218. View

16.

Gnecchi M, He H, Liang O, Melo L, Morello F, Mu H . Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005; 11(4):367-8. DOI: 10.1038/nm0405-367. View

17.

Jackson K, Majka S, Wang H, Pocius J, Hartley C, Majesky M . Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001; 107(11):1395-402. PMC: 209322. DOI: 10.1172/JCI12150. View

18.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

19.

Pagani F, DerSimonian H, Zawadzka A, Wetzel K, Edge A, Jacoby D . Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol. 2003; 41(5):879-88. DOI: 10.1016/s0735-1097(03)00081-0. View

20.

Menasche P, Hagege A, Vilquin J, Desnos M, Abergel E, Pouzet B . Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003; 41(7):1078-83. DOI: 10.1016/s0735-1097(03)00092-5. View