Wiese Danielle M, Wood Catherine A, Braid Lorena R
Aurora BioSolutions Inc., Medicine Hat, AB, Canada.
Simon Fraser University, Burnaby, BC, Canada.
Front Cell Dev Biol. 2022 Apr 13;10:867426. doi: 10.3389/fcell.2022.867426. eCollection 2022.
Retrospective analysis of clinical trial outcomes is a vital exercise to facilitate efficient translation of cellular therapies. These analyses are particularly important for mesenchymal stem/stromal cell (MSC) products. The exquisite responsiveness of MSCs, which makes them attractive candidates for immunotherapies, is a double-edged sword; MSC clinical trials result in inconsistent outcomes that may correlate with underlying patient biology or procedural differences at trial sites. Here we review 45 North American MSC clinical trial results published between 2015 and 2021 to assess whether these reports provide sufficient information for retrospective analysis. Trial reports routinely specify the MSC tissue source, autologous or allogeneic origin and administration route. However, most methodological aspects related to cell preparation and handling immediately prior to administration are under-reported. Clinical trial reports inconsistently provide information about cryopreservation media composition, delivery vehicle, post-thaw time and storage until administration, duration of infusion, and pre-administration viability or potency assessments. In addition, there appears to be significant variability in how cell products are formulated, handled or assessed between trials. The apparent gaps in reporting, combined with high process variability, are not sufficient for retrospective analyses that could potentially identify optimal cell preparation and handling protocols that correlate with successful intra- and inter-trial outcomes. The substantial preclinical data demonstrating that cell handling affects MSC potency highlights the need for more comprehensive clinical trial reporting of MSC conditions from expansion through delivery to support development of globally standardized protocols to efficiently advance MSCs as commercial products.
对临床试验结果进行回顾性分析是促进细胞疗法有效转化的一项重要工作。这些分析对于间充质干/基质细胞（MSC）产品尤为重要。MSC的高度反应性使其成为免疫疗法的有吸引力的候选者，但这也是一把双刃剑；MSC临床试验的结果并不一致，这可能与潜在的患者生物学特征或试验地点的操作差异有关。在此，我们回顾了2015年至2021年间发表的45项北美MSC临床试验结果，以评估这些报告是否为回顾性分析提供了足够的信息。试验报告通常会明确MSC的组织来源、自体或异体来源以及给药途径。然而，大多数与给药前细胞制备和处理相关的方法学方面的内容报告不足。临床试验报告在冷冻保存培养基成分、递送载体、解冻后时间和给药前储存时间、输注持续时间以及给药前活力或效力评估等方面提供的信息不一致。此外，不同试验之间在细胞产品的配制、处理或评估方式上似乎存在很大差异。报告中明显的差距，加上高度的过程变异性，不足以进行回顾性分析，而这种分析可能会确定与试验内和试验间成功结果相关的最佳细胞制备和处理方案。大量临床前数据表明细胞处理会影响MSC的效力，这凸显了需要更全面地报告从扩增到递送的MSC条件的临床试验，以支持制定全球标准化方案，从而有效地将MSC作为商业产品推进。
