Delphi-driven consensus definition for mesenchymal stromal cells and clinical reporting guidelines for mesenchymal stromal cell–based therapeutics

IF 3.7 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotherapy Pub Date : 2025-02-01 DOI:10.1016/j.jcyt.2024.10.008

Laurent Renesme , Kelly D. Cobey , Manoj M. Lalu , Tania Bubela , Raghavan Chinnadurai , John De Vos , Rod Dunbar , Dean Fergusson , Daniel Freund , Jacques Galipeau , Edwin Horwitz , Maxime Lê , Michael Matthay , David Moher , Jan Nolta , Graham Parker , Donald G. Phinney , Mahendra Rao , John E.J. Rasko , Patricia R.M. Rocco , Bernard Thébaud

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引用次数: 0

Abstract

Background aims

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.

Methods

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.

Results

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).

Conclusions

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.

查看原文本刊更多论文

以德尔菲法（Delphi-driven）为基础的间充质基质细胞共识定义和间充质基质细胞疗法临床报告指南。

背景目的：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，但在临床转化方面却面临着巨大的挑战。我们小组的一项范围界定研究强调了造成这一差距的两个关键问题：（i）缺乏对间充质干细胞的明确且一致的定义；（ii）间充质干细胞临床研究中关键参数的报告不足。为了解决这些问题，我们开展了一项修改后的德尔菲研究，以建立和实施一个关于间充质干细胞的共识定义，并制定间充质干细胞临床研究的报告指南：由 22 位国际专家组成的指导委员会参与了三轮德尔菲研究，其中包括来自不同间充质干细胞研究领域的利益相关者。在第一轮中，为了获得广泛的视角，指导委员会推荐的其他研究人员也应邀参加。前两轮采用在线调查的形式，第三轮采用虚拟会议的形式。与会者被要求对一系列潜在的间充质干细胞定义特征和报告指南项目进行评分。达成共识的定义是至少 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），17名参与者参加了第二轮在线调查（2023年秋），15名参与者参加了最终的虚拟共识会议（2024年1月）。就海安会定义而言，共审议了 20 个项目，其中 9 个项目达成了共识。其中包括术语（1 项）、细胞标记表达（5 项）、组织来源（1 项）、干性（1 项）和关键质量属性描述（1 项）。就报告指南而言，加上 28 个初始项目和第一轮中建议的附加项目，共包括 33 个报告项目。其中包括间充质干细胞干预组和对照组（如间充质干细胞产品、剂量和给药）、间充质干细胞特征（如间充质干细胞来源、"适配性"、存活率和免疫兼容性）和间充质干细胞培养条件（如氧气环境、培养基和血清的使用）等项目：这项工作采用德尔菲法为基于间充质干细胞的临床试验确立了一致的间充质干细胞定义和报告指南，在提高间充质干细胞研究的透明度和可重复性方面取得了重大进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotherapy 医学-生物工程与应用微生物

CiteScore

6.30

自引率

4.40%

发文量

683

审稿时长

49 days

期刊介绍： The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.