Cellular therapies for the treatment of immune-mediated GI and liver disease.
Cellular therapies for the treatment of immune-mediated GI and liver disease.
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DOI：
10.1093/bmb/ldaa035
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发表时间：
2020-12
影响因子：
6.7
通讯作者：
Sheeba Khan;R. Khan;P. Newsome
中科院分区：
文献类型：
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作者：
Sheeba Khan;R. Khan;P. Newsome
免疫介导的肝脏和胃肠道疾病是缺乏治愈性治疗的慢性疾病。尽管对这些疾病的理解和治疗取得了进展，但它们通常仍然难以治疗，并且代表了显著的未满足的需求。细胞疗法是一种新兴的选择，有可能产生重大影响。资料来源：采用Pubmed进行文献综述。用于检索的关键词为“ATMP”、“免疫介导的”、“自身免疫性肝病”和“免疫介导的胃肠道疾病”、“细胞治疗”、“MSC”、“HSCT”、“调节性T细胞”、“GVHD”、“乳糜泻”、“IBD”、“PSC”、“AIH”、“PBC”。未生成或分析支持本次审查的新数据。临床试验有大量证据支持使用细胞疗法治疗免疫介导的肝脏和胃肠道疾病。细胞治疗产品有能力“重置”失调的免疫系统，这反过来又可以提供更长期的缓解。目前正在进行间充质基质细胞（MSC）和其他细胞的临床试验，以证明其疗效并填补现有知识的空白。所获得的见解将为未来的试验设计和后续的治疗应用提供信息。争议领域动物研究结果外推至临床试验仍存在一些不确定性。使用细胞疗法后观察到的治疗效果的持久性需要进一步审查。在细胞选择、来源、生产方法和细胞给药方面的异质性对数据的解释提出了挑战。生长点间充质干细胞正在成为免疫介导的肝脏和胃肠道疾病的关键治疗细胞。正在进行的这些细胞的试验将提供新的见解和更好的理解，从而为未来更大规模的研究提供信息。在细胞疗法成为现成的治疗方法之前，仍然需要更大规模的临床试验，以建立在有关细胞疗法安全性和有效性的小型研究证据的基础上。学术界和工业界的一致性，以标准化涉及细胞选择，操作和扩增以及随后在临床试验中的使用的过程，是进一步探索的重要途径。
INTRODUCTION Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact. DATA SOURCES A literature review was carried out using Pubmed. Keywords used for search were 'ATMP', 'immune mediated', 'autoimmune liver disease' and 'immune mediated gastrointestinal conditions', 'cell therapy', 'MSC', 'HSCT', 'Regulatory T cells', 'GVHD', 'Coeliac disease' 'IBD', 'PSC', 'AIH', 'PBC'. No new data were generated or analysed in support of this review. AREAS OF AGREEMENT There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to 'reset' the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications. AREAS OF CONTROVERSY There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data. GROWING POINTS MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies. AREAS TIMELY FOR DEVELOPING RESEARCH Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further.