Laboratório de Pediatria Clínica LIM36, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Instituto de Tratamento de Câncer Infantil, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2023 Aug 14;56:e12647. doi: 10.1590/1414-431X2023e12647. eCollection 2023.
DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.
DiGeorge 综合征是一种由 22 号染色体长臂微缺失引起的疾病。大约 1%的 DiGeorge 综合征患者可能存在功能性胸腺缺失,这是该综合征完全型的特征。这些患者需要紧急治疗来重建 T 细胞免疫。胸腺移植是一种有前途的研究方法,可用于重建先天性无胸腺婴儿的胸腺功能。在这里,我们通过先耗尽胸腺细胞和白细胞细胞谱系,然后用含有保护剂的介质(5%葡聚糖 FP40、5% Me2SO 和 5% FBS)进行冷冻保存,来证明了优化用于移植的胸腺切片制备的可能性,同时保持组织架构。胸腺片段在-196°C 的液氮中储存 30 天或 1 年。片段的组织架构得以保留,包括区分髓质胸腺上皮细胞(TECs)、皮质 TECs 和 Hassall 小体。此外,经过一年冷冻保存的耗尽胸腺片段通过每毫升 3×106 个胸腺细胞的胸腺内注射重新定植,表明这些片段有能力支持 T 细胞发育。因此,这项技术为冷冻和储存大量的胸腺组织以立即移植到 DiGeorge 综合征或非典型(类似于 Omenn)表型的患者中提供了可能性。