Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Australia.
J Tissue Eng Regen Med. 2012 May;6(5):414-20. doi: 10.1002/term.447. Epub 2011 Jul 13.
Tissue engineering involves the use of synthetic or natural materials as a scaffold to support the growth of replacement tissue or organs. The use of autologous cells to populate the scaffold avoids problems associated with rejection; however, a major limitation of this approach is the finite lifespan of primary cells in culture. This finite lifespan is due to the shortening of telomeres, short repetitive sequences of DNA located at the ends of eukaryotic chromosomes. Ectopic expression of telomerase reverse transcriptase (hTERT) is able to reconstitute telomerase activity and maintain the length of telomeres. This study investigated an alternative gene delivery vector, baculovirus, for the expression of hTERT in primary human cells. A recombinant baculovirus was used to efficiently deliver the hTERT gene to primary fibroblasts and the telomerase enzyme was found to be active. Although no increase in telomere length was detected, expression of hTERT in primary fibroblasts resulted in a significant extension of replicative lifespan. To our knowledge this is a novel attempt to use a recombinant baculovirus for the extension of cellular lifespan by exogenous expression of telomerase.
组织工程学涉及使用合成或天然材料作为支架，以支持替代组织或器官的生长。使用自体细胞填充支架可以避免与排斥相关的问题；然而，这种方法的一个主要限制是原代细胞在培养中的有限寿命。这种有限的寿命是由于端粒的缩短，端粒是位于真核染色体末端的短重复 DNA 序列。端粒酶逆转录酶 (hTERT) 的异位表达能够重建端粒酶活性并维持端粒的长度。本研究探讨了一种替代基因传递载体，杆状病毒，用于在原代人细胞中表达 hTERT。使用重组杆状病毒有效地将 hTERT 基因递送至原代成纤维细胞，并且发现端粒酶具有活性。尽管未检测到端粒长度的增加，但 hTERT 在原代成纤维细胞中的表达导致复制寿命显著延长。据我们所知，这是首次尝试使用重组杆状病毒通过端粒酶的外源表达来延长细胞寿命。
