Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy.
Front Immunol. 2021 Feb 10;11:618243. doi: 10.3389/fimmu.2020.618243. eCollection 2020.
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
移植是治疗多种实体器官衰竭的金标准治疗方法,包括肾脏、肝脏、心脏、肺和小肠。定制免疫抑制剂的使用在移植后早期显著提高了移植物和患者的存活率,但由于慢性移植物排斥的发展,长期结果常常不尽如人意,最终导致移植失败。此外,长期免疫抑制会产生严重的副作用,严重影响患者的生存和生活质量。实现耐受,即无需免疫抑制即可稳定的移植物功能,被认为是实体器官移植领域的圣杯。然而,实体同种异体移植物受者中的自发耐受是一种罕见且不可预测的事件。几种策略,包括移植前给予非造血免疫调节细胞,可以在实体器官移植的临床前模型中安全有效地诱导耐受。间充质基质细胞(MSC)是一种可以从几种成人和胎儿组织中获得的非造血细胞,是最有前途的候选者之一。在这篇综述中,我们将重点介绍 MSC 在实体器官移植中的免疫调节作用的当前临床前证据,并讨论其在临床试验中的安全性和有效性的现有证据。