Kregar Velikonja Nevenka, Urban Jill, Fröhlich Mirjam, Neidlinger-Wilke Cornelia, Kletsas Dimitris, Potocar Urska, Turner Sarah, Roberts Sally
Educell Ltd., Prevale 9, Trzin, Slovenia,
Eur Spine J. 2014 Jun;23 Suppl 3:S364-74. doi: 10.1007/s00586-013-3106-9. Epub 2013 Dec 3.
There is increasing interest in the development of cell therapy as a possible approach for the treatment of degenerative disc disease. To regenerate nucleus pulposus tissue, the cells must produce an appropriate proteoglycan-rich matrix, as this is essential for the functioning of the intervertebral disc. The natural environment within the disc is very challenging to implanted cells, particularly if they have been subcultured in normal laboratory conditions. The purpose of this work is to discuss parameters relevant to translating different proposed cell therapies of IVD into clinical use.
Several sources of cells have been proposed, including nucleus pulposus cells, chondrocytes and mesenchymal stem cells derived from bone marrow or adipose tissue. There are some clinical trials and reports of attempts to regenerate nucleus pulposus utilising either autologous or allogenic cells. While the published results of clinical applications of these cell therapies do not indicate any safety issues, additional evidence will be needed to prove their long-term efficacy.
This article discusses parameters relevant for successful translation of research on different cell sources into clinically applicable cell therapies: the influence of the intervertebral disc microenvironment on the cell phenotype, issues associated with cell culture and technical preparation of cell products, as well as discussing current regulatory requirements. There are advantages and disadvantages of each proposed cell type, but no strong evidence to favour any one particular cell source at the moment.
细胞疗法作为治疗椎间盘退变疾病的一种可能方法,其发展受到越来越多的关注。为了使髓核组织再生,细胞必须产生富含蛋白聚糖的合适基质,因为这对椎间盘的功能至关重要。椎间盘内的自然环境对植入细胞极具挑战性,特别是当这些细胞在正常实验室条件下传代培养时。这项工作的目的是讨论与将不同的椎间盘细胞疗法转化为临床应用相关的参数。
已提出多种细胞来源,包括髓核细胞、软骨细胞以及源自骨髓或脂肪组织的间充质干细胞。有一些利用自体或异体细胞再生髓核的临床试验和报道。虽然这些细胞疗法临床应用的已发表结果未表明任何安全问题,但仍需要更多证据来证明其长期疗效。
本文讨论了将不同细胞来源的研究成功转化为临床适用细胞疗法的相关参数:椎间盘微环境对细胞表型的影响、与细胞培养及细胞产品技术制备相关的问题,以及当前的监管要求。每种提议的细胞类型都有其优缺点,但目前尚无有力证据支持某一种特定的细胞来源。