Effect of Exogenously Applied Endothelial Cells in Thymic Regeneration After Hematopoietic Stem Cell Transplantation

外源性内皮细胞对造血干细胞移植后胸腺再生的影响

• 批准号: 411447633
• 负责人: Dr. Hana Andrlova
• 金额: --
• 依托单位: Memorial Sloan Kettering Cancer Center
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/411447633?language=en
• 关键词: Effect; Exogenously; Applied; Endothelial; Cells

Recovery of the immune system after hematopoietic stem cell transplantation is a key process to avoid severe infectious complications and a cancer relapse. Thymic regeneration after an injury, such as chemotherapy, irradiation or graft versus host disease is necessary for regaining the immune competence. The host laboratory recently demonstrated that thymic endothelial cells can be isolated, expanded ex vivo (exECthy) and, when administered intravenously into mice receiving a sub-lethal total body irradiation, enhance thymic recovery. The major goal of the proposed project is to study the adoptive transfer of exECthy as a novel therapeutic approach to improve thymic and immune regeneration in recipients of hematopoietic cell transplantation (HCT). The exECThy isolated from the donor, recipient or a third mouse strain will be injected into mice that have received a syngeneic or allogeneic stem cell transplantation. The effect of this transfer on thymic regeneration, as well as peripheral T-cell reconstitution, T-cell function and T-cell receptor diversity will be evaluated. At the same time, the integration of exECThy in the thymus vasculature and ways to enhance this process will be studied. Adoptive administration of exECThy represents a novel cellular therapy promoting thymic function renewal in patients. Therefore, the results of the proposed project will serve as a starting point for the development of a clinically relevant immune-regenerative strategy.

造血干细胞移植后免疫系统的恢复是避免严重感染并发症和癌症复发的关键过程。损伤后胸腺再生，如化疗、放疗或移植物抗宿主病是恢复免疫能力的必要条件。宿主实验室最近证明，胸腺内皮细胞可以分离，体外扩增（exECthy），当静脉注射到接受亚致死全身照射的小鼠体内时，可以增强胸腺恢复。该项目的主要目标是研究exexthy的过继性转移作为一种新的治疗方法，以改善造血细胞移植（HCT）受者的胸腺和免疫再生。从供体、受体或第三种小鼠中分离出的exexthy将被注射到接受同种或异体干细胞移植的小鼠体内。这种转移对胸腺再生、外周t细胞重建、t细胞功能和t细胞受体多样性的影响将被评估。同时，我们还将研究exECThy在胸腺血管系统中的整合以及如何增强这一过程。exexthy的过继性管理代表了一种促进患者胸腺功能更新的新型细胞疗法。因此，拟议项目的结果将作为临床相关免疫再生策略发展的起点。

项目成果

Early intestinal microbial features are associated with CD4 T cell recovery after allogeneic hematopoietic transplant.

早期肠道微生物特征与同种异体造血移植后 CD4 T 细胞恢复相关

• DOI: 10.1182/blood.2021014255
• 发表时间: 2022
• 期刊: Blood
• 影响因子: 20.3
• 作者: Miltiadous O;Waters NR;Andrlova H;Nguyen CL;Burgos da Silva M;Lindner S;Slingerland J;Giardina P;Clurman A;Armijo GK;Gomes AL;Lakkaraja M;Maslak PG;Scordo M;Shouval R;Staffas A;O'Reilly RJ;Taur Y;Prockop S;Boelens JJ;Giralt S
• 通讯作者: Giralt S