Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease

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• 作者：Ryo Noguchi ; MD^a ; ^{noguchi2@cc.saga-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Koichi Nakayama ; MD ; PhD^b ; Manabu Itoh ; MD^a ; Keiji Kamohara ; MD ; PhD^a ; Kojirou Furukawa ; MD ; PhD^a ; Jun-ichi Oyama ; MD ; PhD^c ; Koichi Node ; MD ; PhD^c ; Shigeki Morita ; MD ; PhD^a
• 关键词：contractile cardiac tissue ; spheroids ; ventricular cardiomyocytes ; dermal fibroblasts ; heart disease
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：35
• 期：1
• 页码：137-145
• 全文大小：6293 K

文摘

The aim of our study was to develop a completely scaffold-free, viable, contractile cardiac tissue capable of being grafted into the damaged native heart.

Methods

Our technology is based on the fundamental characteristics of the self-assembling nature of cells. We created contractile cardiac spheroids by plating a mixture of rat neonatal ventricular cardiomyocytes, human dermal fibroblasts, and human coronary microartery endothelial cells in ultralow attachment plates. First, the optimal cell ratios for the 3 cell sources were determined. Next, approximately 1 × 10⁴ optimal spheroids were fused into a patch-like construct, and the morphologic characteristics and mechanical functions of these patches were evaluated. Finally, the cardiac patches were grafted into the hearts of F344 nude rats, and histologic studies were performed after transplantation.

Results

Synchronous beating of the cardiac patch was confirmed electrophysiologically and mechanically. A micronetwork of endothelial cells was also demonstrated in the construct, and the histologic study performed 5 days after transplantation showed the grafts to be viable, with functioning microvascular structures inside the graft tissue.

Conclusions

We consider the application of our scaffold-free 3-dimensional tissue engineering technology to cardiac regeneration therapy is feasible and expect that this technology will become a promising tool for the treatment of end-stage heart failure.