BIH Center for Regenerative Therapies (BCRT) and Berlin Brandenburg School of Regenerative Therapies (BSRT), Berlin Institute of Health (BIH) at the Charité-Universitätsmedizin Berlin, corporate member of Freie Universität zu Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Roy J. Carver Department of Biomedical Engineering and Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA.
Stem Cells Transl Med. 2022 Mar 3;11(1):2-13. doi: 10.1093/stcltm/szab005.
The number of mesenchymal stromal/stem cell (MSC) therapeutics and types of clinical applications have greatly diversified during the past decade, including rapid growth of poorly regulated "Stem Cell Clinics" offering diverse "Unproven Stem Cell Interventions." This product diversification necessitates a critical evaluation of the reliance on the 2006 MSC minimal criteria to not only define MSC identity but characterize MSC suitability for intravascular administration. While high-quality MSC therapeutics have been safely administered intravascularly in well-controlled clinical trials, repeated case reports of mild-to-more-severe adverse events have been reported. These are most commonly related to thromboembolic complications upon infusion of highly procoagulant tissue factor (TF/CD142)-expressing MSC products. As TF/CD142 expression varies widely depending on the source and manufacturing process of the MSC product, additional clinical cell product characterization and guidelines are needed to ensure the safe use of MSC products. To minimize risk to patients receiving MSC therapy, we here propose to supplement the minimal criteria used for characterization of MSCs, to include criteria that assess the suitability of MSC products for intravascular use. If cell products are intended for intravascular delivery, which is true for half of all clinical applications involving MSCs, the effects of MSC on coagulation and hemocompatibility should be assessed and expression of TF/CD142 should be included as a phenotypic safety marker. This adjunct criterion will ensure both the identity of the MSCs as well as the safety of the MSCs has been vetted prior to intravascular delivery of MSC products.
在过去的十年中，间充质基质/干细胞（MSC）治疗的数量和临床应用的类型大大多样化，包括快速增长的监管不善的“干细胞诊所”提供各种“未经证实的干细胞干预”。这种产品多样化需要对依赖于 2006 年 MSC 最小标准进行严格评估，不仅要定义 MSC 的身份，还要表征 MSC 适合血管内给药的特性。虽然高质量的 MSC 治疗剂已在严格控制的临床试验中安全地进行了血管内给药，但已报告了多次轻度至更严重不良事件的重复病例报告。这些事件最常见于输注高促凝组织因子（TF/CD142）表达 MSC 产品时发生血栓栓塞并发症。由于 TF/CD142 的表达因 MSC 产品的来源和制造工艺而异，因此需要额外的临床细胞产品特征描述和指南，以确保 MSC 产品的安全使用。为了最大限度地降低接受 MSC 治疗的患者的风险，我们在此建议补充用于 MSC 特征描述的最小标准，包括评估 MSC 产品适合血管内使用的标准。如果细胞产品旨在用于血管内输送，这适用于所有涉及 MSC 的临床应用的一半，那么应该评估 MSC 对凝血和血液相容性的影响，并将 TF/CD142 的表达作为表型安全标志物包括在内。这个附加标准将确保在血管内输送 MSC 产品之前，已经对 MSC 的身份和安全性进行了审查。
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