Great Ormond Street Hospital & UCL Great Ormond Street Institute of Child Health.
Department of Immunology, Great Ormond Street Hospital and Department of Molecular and Cellular Immunology, UCL Great Ormond Street Institute of Child Health, London, UK.
Curr Opin Allergy Clin Immunol. 2020 Dec;20(6):541-548. doi: 10.1097/ACI.0000000000000695.
Transplantation of cultured postnatal allogeneic thymus has been successful for treating athymia, mostly associated with complete DiGeorge syndrome, for more than 20 years. Advances in molecular genetics provide opportunities for widening the range of athymic conditions that can be treated while advances in cell culture and organ/tissue regeneration may offer the prospect of alternative preparations of thymic tissue. There are potential broader applications of this treatment outside congenital athymia.
At the same time as further characterization of the cultured thymus product in terms of thymic epithelial cells and lymphoid composition, preclinical studies have looked at de-novo generation of thymic epithelial cells from stem cells and explored scaffolds for delivering these as three-dimensional structures. In the era of newborn screening for T-cell lymphopaenia, a broadening range of defects leading to athymia is being recognized and new assays should allow differentiation of these from haematopoietic cell defects, pending their genetic/molecular characterization. Evidence suggests that the tolerogenic effect of transplanted thymus could be exploited to improve outcomes after solid organ transplantation.
Thymus transplantation, the accepted standard treatment for complete DiGeorge syndrome is also appropriate for other genetic defects leading to athymia. Improved strategies for generating thymus may lead to better outcomes and broader application of this treatment.
将培养的同种异体出生后胸腺移植用于治疗大多数与完全 DiGeorge 综合征相关的先天性无胸腺症已超过 20 年，取得了成功。分子遗传学的进步为扩大可治疗的无胸腺症范围提供了机会，而细胞培养和器官/组织再生的进步可能为胸腺组织的替代制备提供了前景。这种治疗方法除了用于先天性无胸腺症之外，还有可能具有更广泛的应用。
在进一步描述培养的胸腺产物的胸上皮细胞和淋巴组成的同时，临床前研究着眼于从干细胞中重新生成胸腺上皮细胞，并探索用于将这些细胞作为三维结构递送到体内的支架。在新生儿 T 细胞淋巴细胞减少症筛查的时代，越来越多的导致无胸腺症的缺陷被识别出来，新的检测方法应该能够区分这些与造血细胞缺陷，等待其遗传/分子特征确定。有证据表明，移植的胸腺的耐受性效应可以被利用来改善实体器官移植后的结果。
作为治疗完全 DiGeorge 综合征的公认标准治疗方法，胸腺移植也适用于其他导致无胸腺症的遗传缺陷。生成胸腺的改进策略可能会带来更好的结果，并扩大这种治疗方法的应用。
