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J Thorac Cardiovasc Surg 2007;134:1332-1339
© 2007 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Myoblast-based cardiac repair: Xenomyoblast versus allomyoblast transplantation

Changfa Guo, MDa,b, Husnain Kh. Haider, PhDc, Winston S.N. Shim, PhDa,d, Ru-San Tan, MBBSd, Lei Ye, MD, PhDe, Shujia Jiang, MDc, Peter K. Law, PhDf, Philip Wong, MBBSd, Eugene K.W. Sim, FRCSa,g,*

a Department of Surgery, National University of Singapore, Singapore
b Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
c Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio
d National Heart Center, Singapore
e National University Medical Institute, National University of Singapore, Singapore
f Cell Transplants Singapore, Pte Ltd, Singapore
g Gleneagles JPMC Cardiac Center, Brunei Darussalam.

Received for publication March 9, 2007; revisions received July 9, 2007; accepted for publication July 24, 2007.

* Address for reprints: Eugene K. W. Sim, FRCS, B1-12, MD11, National University of Singapore, Singapore 117597. (Email: sursimkw{at}nus.edu.sg).

Objective: We sought to investigate immune cell kinetics in relation to skeletal myoblast survival and heart function improvement after nonautologous skeletal myoblast transplantation in a rat model of myocardial infarction.

Methods: One week after myocardial infarction, 208 Wistar rats were grouped into group 1 (n = 24, receiving 150 µL of medium only), group 2 (n = 24, receiving 150 µL of medium and cyclosporine [INN: ciclosporin]), group 3 (n = 40, human skeletal myoblast transplantation), group 4 (n = 40, human skeletal myoblast transplantation with cyclosporine treatment), group 5 (n = 40, rat skeletal myoblast transplantation), and group 6 (n = 40, rat skeletal myoblast transplantation with cyclosporine treatment). The hearts were harvested at 10 minutes and 1, 4, 7, and 28 days after cell transplantation. Skeletal myoblast survival was confirmed by means of immunohistochemical studies and quantified by using real-time polymerase chain reaction. Host immune responses were assessed by immunostaining for macrophages and CD4+ and CD8+ lymphocytes. Heart function was evaluated by means of echocardiographic analysis.

Results: The majority of macrophages and lymphocytes infiltrated in the acute phase (from day 1 to day 7) and then subsided by day 28. The donor skeletal myoblasts survived and differentiated well in all skeletal myoblast transplantation groups. Allogeneic skeletal myoblasts showed a superior survival rate than xenogeneic skeletal myoblasts (P < .01). Cyclosporine inhibited the infiltration of the immunocytes, enhanced skeletal myoblast survival, and improved heart performance compared with that seen in the groups not receiving cyclosporine treatment (P < .05).

Conclusions: Allomyoblasts survive better than do xenomyoblasts after transplantation into infarcted myocardium. After inhibition of immunocyte infiltration by means of immunosuppressive treatment, skeletal myoblast survival is enhanced, with improved heart performance. These findings suggest the feasibility of nonautologous myoblast transplantation with immunosuppressive treatment.

Abbreviations and Acronyms DAPI = 4',6'-Diamidino-2-phenylindole hydrochloride; DMEM = Dulbecco’s modified Eagle’s medium; EF = ejection fraction; FS = fractional shortening; hSkM = human skeletal myoblast; PCR = polymerase chain reaction; rSkM = rat skeletal myoblast; SkM = skeletal myoblast




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Home page
 Ann. Thorac. Surg.Home page
C. Guo, H. Kh. Haider, C. Wang, R.-S. Tan, W. S.N. Shim, P. Wong, and E. K.W. Sim
Myoblast Transplantation for Cardiac Repair: From Automyoblast to Allomyoblast Transplantation
Ann. Thorac. Surg., December 1, 2008; 86(6): 1841 - 1848.
[Abstract] [Full Text] [PDF]


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