Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products.
Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products.
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DOI：
10.1042/bcj20190382
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发表时间：
2020-09-18
期刊：
影响因子：
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通讯作者：
Dalby MJ
中科院分区：
文献类型：
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作者：
Childs PG;Reid S;Salmeron-Sanchez M;Dalby MJ
自 1995 年首次利用间充质造口/干细胞 (MSC) 进行临床试验以来，已经过去了 25 年。此时学术研究加深了我们对 MSC 生物化学的理解，以及我们使用化学、生物材料和机械方法在体外操纵这些细胞的能力。间充质干细胞可以通过其免疫调节和分化能力来治疗疾病和修复受损组织，这为研究提供了勇气。自1995年以来，已有31种含有间充质干细胞和/或祖细胞的治疗产品进入市场，其体外操作水平差异很大。在这篇综述中，我们总结了现有的含有间充质干细胞或间充质祖细胞的治疗产品，并研究了开发新治疗产品时面临的挑战。成功进入临床试验并最终进入市场，需要在体外临床前开发的最早阶段彻底了解这些障碍。了解新产品的健康经济效益以及各种医疗保健系统内的报销潜力是有益的。应选择临床前研究来证明对人类特定临床适应症的有效性和安全性，以避免重复工作并尽量减少动物使用。还应尽早考虑制造：细胞操作方法如何整合到高度控制的工作流程中，以及如何扩大规模以生产临床相关数量的细胞。最后，我们总结了这些临床产品的主要监管途径，这可以帮助形成早期治疗设计和测试。
Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.