Coutu Daniel L, Yousefi Azizeh-Mitra, Galipeau Jacques
Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada.
J Cell Biochem. 2009 Oct 15;108(3):537-46. doi: 10.1002/jcb.22296.
In the last 20 years, more than 1,500 gene therapy clinical trials have been approved worldwide targeting a variety of indications, from inherited monogenic diseases to acquired conditions such as cancer, cardiovascular and infectious diseases. However, concerns about the safety and efficacy of gene therapy pharmaceuticals justify the development of alternative strategies to ensure the clinical translation of this still promising field. In particular, ex vivo gene therapy strategies using autologous adult stem cells coupled to three-dimensional (3D) porous scaffolds show great promises in preclinical studies. Developments in the fields of biomaterial sciences and tissue engineering have already helped understanding how we can harness to regenerative potential of many cell types to create artificial tissues and organs and vastly improve the engraftment of ex vivo manipulated adult stem cells. In this article, we will review the current state of the art in tissue engineering by exploring the various types of clinically available biomaterials and the methods used to process them into complex 3D scaffolds. We will then review how these technologies are applied in cell-based gene therapy and identify novel avenues of research that may benefit patients in the near future.
在过去20年里，全球已批准1500多项基因治疗临床试验，其针对各种适应症，从遗传性单基因疾病到诸如癌症、心血管疾病和传染病等后天性疾病。然而，对基因治疗药物安全性和有效性的担忧促使人们开发替代策略，以确保这一仍具前景的领域能够实现临床转化。特别是，使用自体成体干细胞与三维（3D）多孔支架相结合的体外基因治疗策略在临床前研究中显示出巨大潜力。生物材料科学和组织工程领域的发展已经有助于我们理解如何利用多种细胞类型的再生潜力来创建人造组织和器官，并极大地改善体外操作的成体干细胞的植入。在本文中，我们将通过探索各种临床可用生物材料的类型以及将它们加工成复杂3D支架的方法，来综述组织工程的当前技术水平。然后，我们将综述这些技术如何应用于基于细胞的基因治疗，并确定在不久的将来可能使患者受益的新研究途径。
