García-Bernal David, García-Arranz Mariano, Yáñez Rosa M, Hervás-Salcedo Rosario, Cortés Alfonso, Fernández-García María, Hernando-Rodríguez Miriam, Quintana-Bustamante Óscar, Bueren Juan A, García-Olmo Damián, Moraleda Jose M, Segovia José C, Zapata Agustín G
Hematopoietic Transplant and Cellular Therapy Unit, Medicine Department, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, University of Murcia, Murcia, Spain.
Spanish Network of Cell Therapy (TerCel), Instituto de Salud Carlos III, Madrid, Spain.
Front Cell Dev Biol. 2021 Mar 16;9:650664. doi: 10.3389/fcell.2021.650664. eCollection 2021.
Mesenchymal stromal cells (MSCs) currently constitute the most frequently used cell type in advanced therapies with different purposes, most of which are related with inflammatory processes. Although the therapeutic efficacy of these cells has been clearly demonstrated in different disease animal models and in numerous human phase I/II clinical trials, only very few phase III trials using MSCs have demonstrated the expected potential therapeutic benefit. On the other hand, diverse controversial issues on the biology and clinical applications of MSCs, including their specific phenotype, the requirement of an inflammatory environment to induce immunosuppression, the relevance of the cell dose and their administration schedule, the cell delivery route (intravascular/systemic vs. local cell delivery), and the selected cell product (i.e., use of autologous vs. allogeneic MSCs, freshly cultured vs. frozen and thawed MSCs, MSCs vs. MSC-derived extracellular vesicles, etc.) persist. In the current review article, we have addressed these issues with special emphasis in the new approaches to improve the properties and functional capabilities of MSCs after distinct cell bioengineering strategies.
间充质基质细胞（MSCs）目前是用于不同目的的先进疗法中最常用的细胞类型，其中大多数与炎症过程有关。尽管这些细胞的治疗效果已在不同疾病动物模型和众多人类I/II期临床试验中得到明确证明，但只有极少数使用MSCs的III期试验证明了预期的潜在治疗益处。另一方面，关于MSCs生物学和临床应用的各种有争议的问题仍然存在，包括它们的特定表型、诱导免疫抑制所需的炎症环境、细胞剂量及其给药方案的相关性、细胞递送途径（血管内/全身给药与局部细胞递送）以及所选细胞产品（即自体与异体MSCs的使用、新鲜培养与冻融MSCs的使用、MSCs与MSCs衍生的细胞外囊泡等）。在当前的综述文章中，我们特别强调了不同细胞生物工程策略后改善MSCs特性和功能能力的新方法，以解决这些问题。
