INSERM UMR643, CHU Hotel-Dieu, 30 boulevard Jean Monnet, Nantes, France.
Curr Opin Organ Transplant. 2012 Feb;17(1):42-7. doi: 10.1097/MOT.0b013e32834ee662.
We discuss the use of tolerogenic dendritic cells (TolDCs) as a therapeutic tool in solid organ transplantation, with particular emphasis on recent experimental and preclinical data supporting the clinical translation of TolDC therapy.
TolDC have been successfully used in rodents to promote long-term allograft survival. Although most studies have focused on donor dendritic cells or donor antigen-pulsed dendritic cells, our group investigated a strategy based on the administration of autologous dendritic cells (not pulsed with donor antigens). We discuss the therapeutic efficacy, mechanisms, and potential risks and advantages of each strategy. We also highlight recent findings on the generation of clinical grade human TolDC from blood monocytes. Finally, we discuss preliminary experience with dendritic cells in humans and critical issues regarding the implementation of TolDC therapy to clinical organ transplantation.
TolDC hold therapeutic promise for the treatment of transplanted patients. Cell therapy with unpulsed, autologous dendritic cells appears as a well tolerated, clinically relevant approach that might help in improving long-term allograft survival and limit the harmful effects of immunosuppressive treatments.
我们讨论了作为实体器官移植治疗工具的耐受性树突状细胞(TolDC)的应用,特别强调了支持 TolDC 治疗临床转化的最新实验和临床前数据。
TolDC 已成功用于促进啮齿动物的长期同种异体移植物存活。尽管大多数研究都集中在供体树突状细胞或供体抗原脉冲的树突状细胞上,但我们小组研究了一种基于给予自体树突状细胞(未用供体抗原脉冲)的策略。我们讨论了每种策略的治疗效果、机制以及潜在风险和优势。我们还重点介绍了最近关于从血液单核细胞生成临床级别的人源 TolDC 的发现。最后,我们讨论了树突细胞在人类中的初步经验以及将 TolDC 治疗应用于临床器官移植的关键问题。
TolDC 为治疗移植患者提供了治疗前景。未脉冲的自体树突状细胞细胞治疗似乎是一种耐受良好、具有临床相关性的方法,有助于改善长期同种异体移植物存活并限制免疫抑制治疗的有害影响。