Ceruso Angela, Gonzalez-Pujana Ainhoa, Igartua Manoli, Santos-Vizcaino Edorta, Hernandez Rosa Maria
NanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain.
Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain.
Drug Deliv Transl Res. 2021 Apr;11(2):498-514. doi: 10.1007/s13346-021-00934-5. Epub 2021 Feb 25.
Mesenchymal stromal cells (MSCs) present the capacity to secrete multiple immunomodulatory factors in response to their microenvironment. This property grants them a golden status among the novel alternatives to treat multiple diseases in which there is an unneeded or exaggerated immune response. However, important challenges still make difficult the clinical implementation of MSC-based therapies, being one of the most remarkable the lack of efficacy due to their transient immunomodulatory effects. To overcome this issue and boost the regulatory potential of MSCs, multiple strategies are currently being explored. Some of them consist of ex vivo pre-conditioning MSCs prior to their administration, including exposure to pro-inflammatory cytokines or to low oxygen concentrations. However, currently, alternative strategies that do not require such ex vivo manipulation are gaining special attention. Among them, the recreation of a three dimensional (3D) environment is remarkable. This approach has been reported to not only boost the immunomodulatory potential of MSCs but also increase their in vivo persistence and viability. The present work revises the therapeutic potential of MSCs, highlighting their immunomodulatory activity as a potential treatment for diseases caused by an exacerbated or unnecessary immune response. Moreover, it offers an updated vision of the most widely employed pre-conditioning strategies and 3D systems intended to enhance MSC-mediated immunomodulation, to conclude discussing the major challenges still to overcome in the field.
间充质基质细胞（MSCs）具有根据其微环境分泌多种免疫调节因子的能力。这一特性使它们在治疗多种存在不必要或过度免疫反应的疾病的新型替代方法中占据了黄金地位。然而，重要的挑战仍然使基于MSC的疗法难以临床应用，其中最显著的问题之一是由于其短暂的免疫调节作用而缺乏疗效。为了克服这个问题并增强MSCs的调节潜力，目前正在探索多种策略。其中一些策略包括在MSCs给药前进行体外预处理，包括暴露于促炎细胞因子或低氧浓度下。然而，目前，不需要这种体外操作的替代策略正受到特别关注。其中，三维（3D）环境的重建尤为突出。据报道，这种方法不仅可以增强MSCs的免疫调节潜力，还可以提高它们在体内的持久性和活力。本工作回顾了MSCs的治疗潜力，强调了它们的免疫调节活性作为治疗由过度或不必要的免疫反应引起的疾病的潜在方法。此外，它提供了对最广泛使用的预处理策略和旨在增强MSC介导的免疫调节的3D系统的最新见解，最后讨论了该领域仍需克服的主要挑战。
