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干细胞移植在牙周再生医学中的转化研究和治疗应用。

Translational research and therapeutic applications of stem cell transplantation in periodontal regenerative medicine.

机构信息

Department of Periodontology and Oral Medicine, School of Stomatology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.

出版信息

Cell Transplant. 2013;22(2):205-29. doi: 10.3727/096368912X656171. Epub 2012 Oct 1.

DOI:10.3727/096368912X656171
PMID:23031442
Abstract

Stem cells have received a great deal of interest from the research community as potential therapeutic "tools" for a variety of chronic debilitating diseases that lack clinically effective therapies. Stem cells are also of interest for the regeneration of tooth-supporting tissues that have been lost to periodontal disease. Indeed, substantial data have demonstrated that the exogenous administration of stem cells or their derivatives in preclinical animal models of periodontal defects can restore damaged tissues to their original form and function. As we discuss here, however, considerable hurdles must be overcome before these findings can be responsibly translated to novel clinical therapies. Generally, the application of stem cells for periodontal therapy in clinics will not be realized until the best cell(s) to use, the optimal dose, and an effective mode of administration are identified. In particular, we need to better understand the mechanisms of action of stem cells after transplantation in the periodontium and to learn how to preciously control stem cell fates in the pathological environment around a tooth. From a translational perspective, we outline the challenges that may vary across preclinical models for the evaluation of stem cell therapy in situations that require periodontal reconstruction and the safety issues that are related to clinical applications of human stem cells. Although clinical trials that use autologous periodontal ligament stem cells have been approved and have already been initiated, proper consideration of the technical, safety, and regulatory concerns may facilitate, rather than inhibit, the clinical translation of new therapies.

摘要

干细胞作为治疗多种慢性进行性疾病的潜在“工具”,受到了研究界的广泛关注,这些疾病缺乏临床有效的治疗方法。干细胞对于牙周病导致的丧失的牙齿支持组织的再生也很有兴趣。事实上,大量数据表明,在牙周缺损的临床前动物模型中,外源性给予干细胞或其衍生物可以将受损组织恢复到原来的形态和功能。然而,正如我们在这里讨论的,在这些发现能够负责任地转化为新的临床治疗方法之前,必须克服相当多的障碍。通常,在临床中应用干细胞进行牙周治疗,直到确定最佳细胞、最佳剂量和有效的给药方式之前,这些发现都无法实现。特别是,我们需要更好地了解移植到牙周组织后干细胞的作用机制,并学习如何在牙齿周围的病理环境中精确控制干细胞的命运。从转化的角度来看,我们概述了在需要牙周重建的情况下,评估干细胞治疗的临床前模型可能存在的挑战,以及与人类干细胞临床应用相关的安全问题。虽然已经批准并已经启动了使用自体牙周韧带干细胞的临床试验,但适当考虑技术、安全和监管问题可能会促进而不是抑制新疗法的临床转化。

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