Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Cardiothoracic Surgery
Published in: Journal of Cardiothoracic Surgery 1/2016

Open Access 01-12-2016 | Research article

Smooth muscle cell sheet transplantation preserve cardiac function and minimize cardiac remodeling in a rat myocardial infarction model

Authors: Shingo Harada, Yoshinobu Nakamura, Suguru Shiraya, Yoshikazu Fujiwara, Yuichiro Kishimoto, Takeshi Onohara, Yuki Otsuki, Satoru Kishimoto, Yasutaka Yamamoto, Ichiro Hisatome, Motonobu Nishimura

Published in: Journal of Cardiothoracic Surgery | Issue 1/2016

Login to get access

Abstract

Background

We examined whether a vascular smooth muscle cell (SMC) sheet is effective in the treatment of a rat myocardial infarction (MI) model.

Methods

We examined the effect of SMC sheet on the cardiac function and cardiac remodeling in a rat MI model in comparison with their effect of dermal fibroblast (DFB) sheet in vivo. Furthermore, we estimated the apoptosis and secretion of angiogenic factor of SMC under hypoxic condition in comparison with DFB. Seven days after MI, monolayer cell sheets were transplanted on the infarcted area (SMC transplantation group, SMC-Tx; DFB transplantation group, DFB-Tx; no cell sheet transplantation group, Untreated; neither MI nor cell sheet transplantation group, Sham). We evaluated cardiac function by echocardiogram, degree of cardiac remodeling by histological examination, and secretion of angiogenic growth factor by enzyme immunoassay.

Results

Twenty-eight days after transplantation, SMC-Tx showed the following characteristics compared with the other groups: 1) significantly greater fractional area shortening (SMC-Tx, 32.3 ± 2.1 %; DFB-Tx, 23.3 ± 2.1 %; untreated, 25.1 ± 2.6 %), 2) suppressed left ventricular dilation, smaller scar expansion, and preserved wall thickness of the area at risk and the posterior wall, 3) decreased fibrosis, preserved myocardium in the scar area, and greater number of arterioles in border-zone, 4) tight attachment of SMC sheets on the scarred myocardium, and less apoptotic cell death. In in vitro experiments, SMCs secreted higher amounts of basic fibroblast growth factor (SMC, 157.7 ± 6.4 pg/ml; DFB, 3.1 ± 1.0 pg/ml), and showed less apoptotic cell death under hypoxia.

Conclusions

Our results illustrate that transplantation of SMC sheets inhibited the progression of cardiac remodeling and improve cardiac function. These beneficial effects may be due to superior SMC survival.
Literature
1.
Nishida M, Li TS, Hirata K, Yano M, Matsuzaki M, Hamano K. Improvement of cardiac function by bone marrow cell implantation in a rat hypoperfusion heart model. Ann Thorac Surg. 2003;75(3):768–73.CrossRefPubMed
2.
Nagaya N, Kangawa K, Itoh T, et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 2005;112(8):1128–35.CrossRefPubMed
3.
Jain M, DerSimonian H, Brenner DA, et al. Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation. 2001;103(14):1920–7.CrossRefPubMed
4.
Yasuda T, Weisel RD, Kiani C, Mickle DA, Maganti M, Li RK. Quantitative analysis of survival of transplanted smooth muscle cells with real-time polymerase chain reaction. J Thorac Cardiovasc Surg. 2005;129(4):904–11.CrossRefPubMed
5.
Ziebart T, Yoon CH, Trepels T, et al. Sustained persistence of transplanted proangiogenic cells contributes to neovascularization and cardiac function after ischemia. Circ Res. 2008;103(11):1327–34.CrossRefPubMed
6.
Yang J, Yamato M, Kohno C, et al. Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials. 2005;26(33):6415–22.CrossRefPubMed
7.
Shimizu T, Yamato M, Kikuchi A, Okano T. Cell sheet engineering for myocardial tissue reconstruction. Biomaterials. 2003;24(13):2309–16.CrossRefPubMed
8.
Memon IA, Sawa Y, Fukushima N, et al. Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets. J Thorac Cardiovasc Surg. 2005;130(5):1333–41.CrossRefPubMed
9.
Miyahara Y, Nagaya N, Kataoka M, et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med. 2006;12(4):459–65.CrossRefPubMed
10.
Sawa Y, Yoshikawa Y, Toda K. Safety and efficacy of autologous skeletal myoblast sheets (TCD-51073) for the treatment of severe chronic heart failure due to ischemic heart disease. Circ J. 2015;79(5):991–9.CrossRefPubMed
11.
Ali S, Becker MW, Davis MG, Dorn 2nd GW. Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C. Circ Res. 1994;75(5):836–43.CrossRefPubMed
12.
Stavri GT, Zachary IC, Baskerville PA, Martin JF, Erusalimsky JD. Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia. Circulation. 1995;92(1):11–4.CrossRefPubMed
13.
Hobo K, Shimizu T, Sekine H, Shin’oka T, Okano T, Kurosawa H. Therapeutic angiogenesis using tissue engineered human smooth muscle cell sheets. Arterioscler Thromb Vasc Biol. 2008;28(4):637–43.CrossRefPubMed
14.
Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.CrossRefPubMed
15.
Li RK, Jia ZQ, Weisel RD, Merante F, Mickle DA. Smooth muscle cell transplantation into myocardial scar tissue improves heart function. J Mol Cell Cardiol. 1999;31(3):513–22.CrossRefPubMed
16.
Liu TB, Fedak PW, Weisel RD, et al. Enhanced IGF-1 expression improves smooth muscle cell engraftment after cell transplantation. Am J Physiol Heart Circ Physiol. 2004;287(6):H2840–9.CrossRefPubMed
17.
Nakamura Y, Yasuda T, Weisel RD, Li RK. Enhanced cell transplantation: preventing apoptosis increases cell survival and ventricular function. Am J Physiol Heart Circ Physiol. 2006;291(2):H939–47.CrossRefPubMed
18.
Matsubayashi K, Fedak PW, Mickle DA, Weisel RD, Ozawa T, Li RK. Improved left ventricular aneurysm repair with bioengineered vascular smooth muscle grafts. Circulation. 2003;108 Suppl 1:II219–25.PubMed
19.
Atluri P, Liao GP, Panlilio CM, et al. Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Ann Thorac Surg. 2006;81(5):1728–36.CrossRefPubMed
20.
Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004;114(3):330–8.CrossRefPubMedPubMedCentral
21.
22.
Wang T, Wu DQ, Jiang XJ, et al. Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling. Eur J Heart Fail. 2009;11(1):14–9.CrossRefPubMed
23.
Oz MC, Konertz WF, Kleber FX, et al. Global surgical experience with the Acorn cardiac support device. J Thorac Cardiovasc Surg. 2003;126(4):983–91.CrossRefPubMed
24.
Blom AS, Mukherjee R, Pilla JJ, et al. Cardiac support device modifies left ventricular geometry and myocardial structure after myocardial infarction. Circulation. 2005;112(9):1274–83.CrossRefPubMed
25.
Sekine H, Shimizu T, Hobo K, et al. Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances neovascularization and improves cardiac function of ischemic hearts. Circulation. 2008;118(14):S145–52.CrossRefPubMed
26.
Hamdi H, Furuta A, Bellamy V, et al. Cell delivery: intramyocardial injections or epicardial deposition? A head-to-head comparison. Ann Thorac Surg. 2009;87(4):1196–203.CrossRefPubMed
27.
Kondoh H, Sawa Y, Miyagawa S, et al. Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters. Cardiovasc Res. 2006;69(2):466–75.CrossRefPubMed
28.
Nishida K, Yamato M, Hayashida Y, et al. Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface. Transplantation. 2004;77(3):379–85.CrossRefPubMed
29.
Akizuki T, Oda S, Komaki M, et al. Application of periodontal ligament cell sheet for periodontal regeneration: a pilot study in beagle dogs. J Periodontal Res. 2005;40(3):245–51.CrossRefPubMed
30.
Hayashida Y, Nishida K, Yamato M, et al. Ocular surface reconstruction using autologous rabbit oral mucosal epithelial sheets fabricated ex vivo on a temperature-responsive culture surface. Invest Ophthalmol Vis Sci. 2005;46(5):1632–9.CrossRefPubMed
31.
Shiroyanagi Y, Yamato M, Yamazaki Y, Toma H, Okano T. Urothelium regeneration using viable cultured urothelial cell sheets grafted on demucosalized gastric flaps. BJU Int. 2004;93(7):1069–75.CrossRefPubMed
Metadata
Title
Smooth muscle cell sheet transplantation preserve cardiac function and minimize cardiac remodeling in a rat myocardial infarction model
Authors
Shingo Harada
Yoshinobu Nakamura
Suguru Shiraya
Yoshikazu Fujiwara
Yuichiro Kishimoto
Takeshi Onohara
Yuki Otsuki
Satoru Kishimoto
Yasutaka Yamamoto
Ichiro Hisatome
Motonobu Nishimura
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Cardiothoracic Surgery / Issue 1/2016
Electronic ISSN: 1749-8090
DOI
https://doi.org/10.1186/s13019-016-0508-x

Other articles of this Issue 1/2016

Journal of Cardiothoracic Surgery 1/2016 Go to the issue

Case report

Pitfalls in the management of isolated pulmonary Takayasu’s arteritis after surgery: a case report of an experience during 34 months after a pulmonary artery graft replacement

Research article

An assessment of outcomes with intramedullary fixation of fractured ribs

Research article

Can predilatation in transcatheter aortic valve implantation be omitted? - a prospective randomized study

Research article

Image quality and radiation dose of dual-source CT cardiac angiography using prospective ECG-triggering technique in pediatric patients with congenital heart disease

Case report

Bilateral single-port thoracoscopic extended thymectomy for management of thymoma and myasthenia gravis: case report

Research article

The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis: intermediate-term efficacy and durability