Department of Oncological Surgery, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, China.
Biomed Pharmacother. 2024 Nov;180:117537. doi: 10.1016/j.biopha.2024.117537. Epub 2024 Oct 13.
Mesenchymal stromal cells (MSCs) exhibit significant potential in the context of cell therapy because of their capacity to perform a range of interconnected functions in damaged tissues, including immune modulation, hematopoietic support, and tissue regeneration. MSCs are hypoimmunogenic because of their diminished expression of major histocompatibility molecules, absence of costimulatory molecules, and presence of coinhibitory molecules. While autologous MSCs reduce the risk of rejection and infection, variability in cell numbers and proliferation limits their potential applications. Conversely, allogeneic MSCs (allo-MSCs) possess broad clinical applications unconstrained by donor physiology. Nonetheless, preclinical and clinical investigations highlight that transplanted allo-MSCs are subject to immune attack from recipients. These cells exhibit anti-inflammatory and proinflammatory phenotypes contingent on the microenvironment. Notably, the proinflammatory phenotype features enhanced immunogenicity and diminished immunosuppression, potentially triggering allogeneic immune reactions that impede long-term clinical efficacy. Consequently, preserving the low immunogenicity of allo-MSCs in vivo and mitigating immune rejection in diverse microenvironments represent crucial challenges for the widespread clinical application of MSCs. In this review, we elucidate the immune regulation of allo-MSCs, specifically focusing on two distinct subgroups, MSC1 and MSC2, that exhibit varying polarization states and immunogenicity. We discuss the factors and underlying mechanisms that induce MSC immunogenicity and polarization, highlighting the crucial role of major histocompatibility complex class I/II molecules in rejection post-transplantation. Additionally, we summarize the immunogenic regulatory targets and applications of allo-MSCs and outline strategies to address challenges in this promising field, aiming to enhance allo-MSC therapeutic efficacy for patients.
间充质基质细胞 (MSCs) 在细胞治疗方面具有显著的潜力，因为它们能够在受损组织中发挥一系列相互关联的功能，包括免疫调节、造血支持和组织再生。MSCs 的主要组织相容性分子表达降低、缺乏共刺激分子和存在共抑制分子，因此具有低免疫原性。虽然自体 MSCs 降低了排斥和感染的风险，但细胞数量和增殖的可变性限制了它们的潜在应用。相反，同种异体 MSCs (allo-MSCs) 具有广泛的临床应用，不受供体生理的限制。尽管如此，临床前和临床研究强调，移植的 allo-MSCs 会受到受体的免疫攻击。这些细胞表现出抗炎和促炎表型，这取决于微环境。值得注意的是，促炎表型的特点是免疫原性增强和免疫抑制作用减弱，可能引发同种异体免疫反应，从而阻碍长期的临床疗效。因此，在体内保持 allo-MSCs 的低免疫原性，并减轻不同微环境中的免疫排斥，是 MSCs 广泛临床应用的关键挑战。在这篇综述中，我们阐明了 allo-MSCs 的免疫调节，特别是关注两种不同的亚群，MSC1 和 MSC2，它们表现出不同的极化状态和免疫原性。我们讨论了诱导 MSC 免疫原性和极化的因素和潜在机制，强调了主要组织相容性复合体 I/II 分子在移植后排斥中的关键作用。此外，我们总结了 allo-MSCs 的免疫调节靶点和应用，并概述了应对这一充满希望领域挑战的策略，旨在提高 allo-MSC 对患者的治疗效果。
