Renesme Laurent, Cobey Kelly D, Lalu Manoj M, Bubela Tania, Chinnadurai Raghavan, De Vos John, Dunbar Rod, Fergusson Dean, Freund Daniel, Galipeau Jacques, Horwitz Edwin, Lê Maxime, Matthay Michael, Moher David, Nolta Jan, Parker Graham, Phinney Donald G, Rao Mahendra, Rasko John E J, Rocco Patricia R M, Rossi Fabio, Myles Michael Rosu, Viswanathan Sowmya, Thébaud Bernard
Sinclair Center for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Canada; Neonatology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
University of Ottawa Heart Institute, Ottawa, Canada.
Cytotherapy. 2025 Feb;27(2):146-168. doi: 10.1016/j.jcyt.2024.10.008. Epub 2024 Oct 29.
Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies.
A steering committee of 22 international experts, including stakeholders from different MSC research fields, participated in the three Delphi rounds. For the first round, to obtain a broad perspective, additional investigators recommended by the steering committee were invited to participate. The first two rounds consisted of online surveys, whereas the third round took the form of a virtual meeting. Participants were asked to rate a series of potential defining characteristics of MSCs and items for reporting guidelines. Consensus was defined as at least 80% of the participants rating the item in the same category of importance.
Eighty-seven international participants participated in the first round survey (spring 2023), 17 participants participated in the second online survey (fall 2023) and 15 participants participated in the final virtual consensus meeting (January 2024). For the MSC definition, 20 items were considered and nine reached consensus. Items included terminology (one item), cell marker expression (five items), tissue origin (one item), stemness (one item) and description of critical quality attributes (one item). For the reporting guidelines, with the 28 initial items and the additional items suggested during round 1, a total of 33 items to report were included. This included items on MSC intervention group and control (e.g., MSC product, dose and administration), MSC characteristics (e.g., MSC provenance, "fitness," viability and immune compatibility) and MSC culture conditions (e.g., oxygen environment, culture medium and use of serum).
By applying a Delphi method to establish a consensus definition for MSCs and reporting guidelines for MSC-based clinical trials, this work represents a significant advance in improving transparency and reproducibility in the conduct and reporting of MSC research.
尽管间充质基质细胞（MSCs）在临床前研究中取得了令人鼓舞的结果，但在临床转化方面面临重大挑战。我们团队的一项范围综述强调了造成这一差距的两个关键问题：（i）缺乏关于MSCs的明确且一致的定义；（ii）MSCs临床研究中关键参数报告不足。为解决这些问题，我们开展了一项改良的德尔菲研究，以建立并实施MSCs的共识定义，并制定MSCs临床研究的报告指南。
一个由22名国际专家组成的指导委员会，包括来自不同MSCs研究领域的利益相关者，参与了三轮德尔菲研究。在第一轮中，为了获得更广泛的观点，邀请了指导委员会推荐的其他研究人员参与。前两轮采用在线调查的形式，而第三轮采取虚拟会议的形式。参与者被要求对一系列MSCs的潜在定义特征以及报告指南的项目进行评分。共识被定义为至少80%的参与者将该项目评为同一重要类别。
87名国际参与者参加了第一轮调查（2023年春季），17名参与者参加了第二轮在线调查（2023年秋季），15名参与者参加了最后的虚拟共识会议（2024年1月）。对于MSCs的定义，共考虑了20项，其中9项达成了共识。这些项目包括术语（1项）、细胞标志物表达（5项）、组织来源（1项）、干性（1项）以及关键质量属性的描述（1项）。对于报告指南，结合最初的28项以及第一轮中提出的其他项目，总共纳入了33项需要报告的内容。这包括关于MSCs干预组和对照组的项目（例如，MSCs产品、剂量和给药方式）、MSCs特征（例如，MSCs来源、“健康状况”、活力和免疫相容性）以及MSCs培养条件（例如，氧气环境、培养基和血清的使用）。
通过应用德尔菲方法建立MSCs的共识定义和基于MSCs的临床试验报告指南，这项工作在提高MSCs研究的开展和报告的透明度及可重复性方面取得了重大进展。
