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J Thorac Cardiovasc Surg 2007;134:65-73
© 2007 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Tissue regeneration observed in a basic fibroblast growth factor–loaded porous acellular bovine pericardium populated with mesenchymal stem cells

Yen Chang, MDa, Po-Hong Lai, PhDb, Hao-Ji Wei, MDa, Wei-Wen Lin, MDc, Chun-Hung Chen, MSb, Shiaw-Min Hwang, PhDd, Sung-Ching Chen, PhDb, Hsing-Wen Sung, PhDb,*

a Division of Cardiovascular Surgery, Veterans General Hospital-Taichung and College of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
b Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
c Division of Cardiology, Veterans General Hospital-Taichung and Department of Life Science, Tunghai University, Taichung, Taiwan, R.O.C.
d Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, R.O.C.

Received for publication November 10, 2006; revisions received February 1, 2007; accepted for publication February 6, 2007.

* Address for reprints: Professor Hsing-Wen Sung, PhD, Department of Chemical Engineering/Bioengineering Program, National Tsing Hua University, Hsinchu, Taiwan 30013. (Email: hwsung{at}che.nthu.edu.tw).

Objective: We sought to induce tissue regeneration within a porous patch for repair of a myocardial defect.

Methods: A basic fibroblast growth factor–loaded porous bovine pericardium populated with 5-bromo-2'-deoxyuridine–labeled mesenchymal stem cells was used as a cardiac patch (the basic fibroblast growth factor/mesenchymal stem cell patch) to repair a defect created in a syngeneic rat model. The blank porous pericardium (the control patch) and the patch loaded with basic fibroblast growth factor were used as controls. The implanted patches were retrieved at 4 and 12 weeks postoperatively (n = 5 per group at each time point).

Results: At retrieval, we found that none of the patches were thinned or dilated. Endothelialization and remesothelialization were observed on the endocardial and epicardial surfaces of patches in each of the studied groups, respectively. Additionally, newly regenerated muscle fibers, glycosaminoglycans, smooth muscle cells, and microvessels were seen in the middle layers of all patches, an indication of tissue regeneration. However, the extents of tissue regeneration in the basic fibroblast growth factor and basic fibroblast growth factor/mesenchymal stem cell patches were more pronounced than in those of the control patch. This may be attributed to the fact that the densities of neomicrovessels observed in the basic fibroblast growth factor and basic fibroblast growth factor/mesenchymal stem cell patches were significantly greater than in those of the control patch. 5-Bromo-2'-deoxyuridine–labeled cardiomyocytes, smooth muscle cells, and endothelial cells were identified in the basic fibroblast growth factor/mesenchymal stem cells patch, and no cardiomyocytes were observed in the control and basic fibroblast growth factor patches.

Conclusion: The results provided evidence of tissue regeneration within a porous bovine pericardium through a process involving cell recruitment and tissue-specific differentiation.

Abbreviations and Acronyms 5-aza = 5-azacytidine; {alpha}-SMA = {alpha}-smooth muscle actin; bFGF = basic fibroblast growth factor; BrdU = 5-bromo-2'-deoxyuridine; ECM = extracellular matrix; EVG = elastic van Gieson; GAG = glycosaminoglycan; H&E = hematoxylin and eosin; MSC = mesenchymal stem cell; SEM = scanning electron microscopic; SMC = smooth muscle cell






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