National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.
Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Semin Liver Dis. 2020 Nov;40(4):411-426. doi: 10.1055/s-0040-1717096. Epub 2020 Dec 24.
Over the last decade, there has been a considerable progress in the development of cell therapy products for the treatment of liver diseases. The quest to generate well-defined homogenous cell populations with defined mechanism(s) of action has enabled the progression from use of autologous bone marrow stem cells comprising of heterogeneous cell populations to allogeneic cell types such as monocyte-derived macrophages, regulatory T cells, mesenchymal stromal cells, macrophages, etc. There is growing evidence regarding the multiple molecular mechanisms pivotal to various therapeutic effects and hence, careful selection of cell therapy product for the desired putative effects is crucial. In this review, we have presented an overview of the cell therapies that have been developed thus far, with preclinical and clinical evidence for their use in liver disease. Limitations associated with these therapies have also been discussed. Despite the advances made, there remain multiple challenges to overcome before cell therapies can be considered as viable treatment options, and these include larger scale clinical trials, scalable production of cells according to good manufacturing practice standards, pathways for delivery of cell therapy within hospital environments, and costs associated with the production.
在过去的十年中,细胞治疗产品在治疗肝脏疾病方面取得了相当大的进展。人们一直在努力开发具有明确作用机制的同质细胞群体,这使得从使用包含异质细胞群体的自体骨髓干细胞进展到同种异体细胞类型,如单核细胞衍生的巨噬细胞、调节性 T 细胞、间充质基质细胞、巨噬细胞等。越来越多的证据表明,多种分子机制对各种治疗效果至关重要,因此,仔细选择细胞治疗产品以获得所需的假定效果至关重要。在这篇综述中,我们介绍了迄今为止开发的细胞疗法,并提供了它们在肝脏疾病中的临床前和临床证据。我们还讨论了这些疗法的局限性。尽管取得了进展,但在细胞疗法被认为是可行的治疗选择之前,仍有多个挑战需要克服,其中包括更大规模的临床试验、根据良好生产规范标准规模化生产细胞、在医院环境中输送细胞疗法的途径以及与生产相关的成本。