Collart-Dutilleul Pierre-Yves, Chaubron Franck, De Vos John, Cuisinier Frédéric J
Pierre-Yves Collart-Dutilleul, Frédéric J Cuisinier, BioNano Laboratory EA 4203, Montpellier 1 University, 34193 Montpellier Cedex5, France.
World J Stem Cells. 2015 Aug 26;7(7):1010-21. doi: 10.4252/wjsc.v7.i7.1010.
Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.
再生医学和基于细胞的治疗领域的医学研究为干细胞在临床试验中的应用带来了令人鼓舞的前景。人们已经对多种类型的干细胞进行了研究，从祖细胞到多能干细胞。其中，牙髓干细胞（DPSCs）是源自牙髓的间充质多能细胞，牙髓是牙齿内部的软组织。它们是一种有趣的成体干细胞来源，因为与其他成体干细胞来源相比，通过非侵入性技术可以从牙髓中大量获取。DPSCs可以从废弃牙齿中获得，尤其是因正畸原因拔除的智齿。为了从有前景的临床前结果转向人类治疗应用，DPSCs必须以临床级批量制备并转化为高级治疗药品（ATMP）。由于生产患者特异性干细胞成本高且耗时，临床级人类白细胞抗原（HLA）分型的DPSC系的同种异体生物样本库提供了高效的创新治疗产品。DPSC生物样本库通过将废弃的生物组织（牙髓）用作间充质干细胞的来源，在良好生产规范（GMP）条件下生产和储存DPSC治疗批次，代表了工业和治疗方面的创新。在这篇综述中，我们讨论了按照法规、GMP指南和伦理原则将生物样本从供体转移到HLA分型的DPSC治疗批次所面临 的挑战。我们还介绍了一些目前尚无有效治疗方法，但基于DPSCs的ATMP可能有潜在治疗作用的临床应用。
