Division of Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
Division of Hematology, University Hospitals Ghent, Ghent, Belgium.
Blood Rev. 2021 Jan;45:100718. doi: 10.1016/j.blre.2020.100718. Epub 2020 May 29.
Bone marrow-derived multipotent mesenchymal stromal cells (BM-MSCs) are non-haematopoietic cells present in the bone marrow stroma. They have the potential to modulate immune responses and exhibit a capacity to promote immune tolerance. Although the efficacy of immunosuppressive drugs has improved significantly, thereby ameliorating renal graft outcome, the use of these drugs still carries an increased risk of malignancies and opportunistic infections, and sometimes fail to prevent chronic allograft rejection or recurrence of the original kidney disease. As such, there is strong interest in ways to induce immune tolerance and thereby tempering or avoiding conventional immunosuppressive drugs. Cellular immunomodulation by MSCs can create a new way to induce transplant tolerance. This review will give a critical overview of the use of BM-MSCs as a cell-based immunosuppressive therapy in kidney transplant recipients. In vitro studies revealed several mechanisms that can clarify the immunomodulatory potential of BM-MSCs. Several clinical studies showed that BM-MSCs can modulate T-cell proliferation and can alter the ratio of T-cell subsets, favoring immune tolerance. However, this immunomodulation was often not associated with better clinical outcome during follow-up when compared to control groups. Some clinical studies found that BM-MSCs allow a reduction in dose of conventional immunosuppressive drugs and prevent acute graft dysfunction. Most clinical studies emphasized that BM-MSC infusion was safe. This review suggests that the use of BM-MSCs as cell-based immunosuppression therapy in kidney transplant recipients has potential, however some caution regarding their clinical use is appropriate. Mechanisms by which BM-MSCs induce transplant tolerance and factors that can alter their functionality need to be analyzed in more detail before clinical use.
骨髓来源的多能间充质基质细胞（BM-MSCs）是存在于骨髓基质中的非造血细胞。它们具有调节免疫反应的潜力，并表现出促进免疫耐受的能力。尽管免疫抑制药物的疗效有了显著提高，从而改善了肾移植的结果，但这些药物的使用仍然存在增加恶性肿瘤和机会性感染的风险，有时甚至不能预防慢性移植物排斥反应或原肾病的复发。因此，人们强烈关注诱导免疫耐受的方法，从而缓和或避免使用传统的免疫抑制剂。MSC 的细胞免疫调节可以为诱导移植耐受开辟新途径。本综述将对 BM-MSCs 作为细胞免疫抑制疗法在肾移植受者中的应用进行批判性评价。体外研究揭示了几种可以阐明 BM-MSCs 免疫调节潜力的机制。几项临床研究表明，BM-MSCs 可以调节 T 细胞增殖，并可以改变 T 细胞亚群的比例，有利于免疫耐受。然而，与对照组相比，在随访期间，这种免疫调节通常与更好的临床结果无关。一些临床研究发现，BM-MSCs 可以减少常规免疫抑制剂的剂量，并预防急性移植物功能障碍。大多数临床研究强调 BM-MSC 输注是安全的。本综述表明，BM-MSCs 作为细胞免疫抑制疗法在肾移植受者中的应用具有潜力，但在临床应用中需要适当谨慎。在临床应用之前，需要更详细地分析 BM-MSCs 诱导移植耐受的机制以及可以改变其功能的因素。
