Nakashima Misako, Iohara Koichiro, Zheng Li
Laboratory of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi 474-8522, Japan.
Curr Gene Ther. 2006 Oct;6(5):551-60. doi: 10.2174/156652306778520665.
Recent advances in stem cell biology and gene therapy technology have provided the great potential of adult stem cells for therapeutic use in regeneration of lost tissue due to diseases including cancer, trauma, and even caries. Dental pulp tissues harbor mesenchymal stem/progenitor cells and have potential to regenerate and/or repair dentin-pulp complex after injury such as caries. There are two main methods, in vivo and ex vivo gene therapy. In in vivo gene therapy the healing potential of pulp tissue is enhanced by genes inducing dentin directly applied on the exposed/amputated dental pulp. In ex vivo gene therapy, pulp stem/progenitor cells transfected with some therapeutically proven genes to induce differentiation into odontoblasts which are transplanted on the exposed/amputated pulp. In the inflamed pulp under deep caries or trauma, possibly due to the limited supply of pulp stem/progenitor cells, it might be useful to apply cell-based ex vivo gene therapy compared to in vivo gene therapy. Before clinical use of ex vivo gene therapy for dentin regeneration in endodontics, there is a need for establishment of isolation, identification and expansion of the pulp stem cells. A safe and efficient gene delivery system also needs to be optimized. In this review we provide an overview of our current knowledge in the biology and function of adult pulp stem cells. This is followed by a discussion of the challenges of translating basic cellular and molecular biology of differentiation of pulp stem cells to safe and efficient gene therapy for dentin regeneration.
干细胞生物学和基因治疗技术的最新进展为成体干细胞在治疗因癌症、创伤甚至龋齿等疾病导致的组织缺失方面提供了巨大潜力。牙髓组织含有间充质干/祖细胞，在龋齿等损伤后有再生和/或修复牙本质-牙髓复合体的潜力。基因治疗主要有两种方法，即体内基因治疗和体外基因治疗。在体内基因治疗中，通过将直接诱导牙本质形成的基因应用于暴露/切断的牙髓来增强牙髓组织的愈合潜力。在体外基因治疗中，用一些经治疗验证的基因转染牙髓干/祖细胞，诱导其分化为成牙本质细胞，然后将这些细胞移植到暴露/切断的牙髓上。在深龋或创伤引起的炎症牙髓中，可能由于牙髓干/祖细胞的供应有限，与体内基因治疗相比，应用基于细胞的体外基因治疗可能更有用。在将体外基因治疗临床应用于牙髓病学中的牙本质再生之前，需要建立牙髓干细胞的分离、鉴定和扩增方法。还需要优化安全有效的基因传递系统。在这篇综述中，我们概述了目前关于成体牙髓干细胞生物学和功能的知识。随后讨论了将牙髓干细胞分化的基础细胞和分子生物学转化为安全有效的牙本质再生基因治疗所面临的挑战。
