結合組織工程及基因治療的概念，可使具有修復功能的軟骨組織塊更快被取得，並能植回病人患處進行組織的重建。由於桿狀病毒本身的優異性，使其在近年來逐步發展成為新興的基因傳送載體。本實驗室先前已證實體外 (in vitro) 培養的軟骨細胞可成功地被桿狀病毒所轉導，且其轉導效率高達88%左右，顯示桿狀病毒可作為基因傳送載體並應用於軟骨組織工程中。然而，短暫的基因表現卻限制了桿狀病毒的應用性。為延長轉殖基因在細胞內的表現時間，本研究擬利用重複轉導 (supertransduction) 策略以驅使細胞持續表現外來基因。但是，重複轉導的效果卻較初次轉導 (initial transduction) 為差。實驗發現，除了細胞所分泌的細胞外間質 (extra-cellular matrix) 會阻礙病毒的進入外，我們也首次提出桿狀病毒的轉導效率與細胞週期 (cell cycle) 間的關係。本研究證實，桿狀病毒進入細胞的效率不因細胞處於不同間期 (phase) 而有所改變，但G2/M phase細胞有利外來基因的表現，反之外來基因在G0/G1A phase細胞內的表現情況最差。進一步探究原因後發現，在G0/G1A phase細胞內，病毒被傳送至細胞核的效率不佳，且轉殖基因也產生較嚴重的甲基化現象，因而導致重複轉導時的基因表現受到抑制。此外，本研究更進一步剖析桿狀病毒應用於組織工程上的安全性疑慮等問題。我們發現，桿狀病毒轉導軟骨細胞會誘發IFN-α/β、TNF-α及IL-6等細胞激素 (cytokine) 的表現，其中IFN會使細胞產生抗病毒機制 (antiviral effect)，進而抑制轉殖基因的表現。然而，這些負面效應會隨著細胞培養時間的拉長而逐漸遞減並回復常態，因此，在適當的時間點施行重複轉導策略可短暫延長基因表現，並達到刺激軟骨細胞分化的目的。

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