Organ Transplant Center of the First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology,Guangdong Provincial International Cooperation Base of Science and Technology(Organ Transplantation), Guangzhou, China.
Reproductive Medicine Center of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Stem Cell Res Ther. 2017 Nov 21;8(1):266. doi: 10.1186/s13287-017-0712-1.
This study aimed to investigate the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and to confirm the low immunogenicity of hepatocytes differentiated from ESCs.
Green fluorescent protein-labeled ESCs collected from 129 mice were cultured to differentiate into hepatocytes. smDCs and regDCs were cultured in vitro. The hepatocytes were cultured after being extracted from the livers of 129 mice. After injecting smDCs or regDCs 3 days in advance, these differentiated hepatocytes and normal hepatocytes were transplanted into the livers of BALB/c mice separately. Subsequently, the histopathological features and cytokines in transplant tissues as well as the Foxp3 expression in peripheral blood CD4 T cells of the recipients were examined.
The morphological phenotypes of smDCs and regDCs were similar. They both expressed medium levels of MHC-II, CD40, CD80, and CD86, high levels of TGF-β and IL-10, and low levels of IL-2. The survival of differentiated hepatocytes was prolonged and inflammatory infiltration in transplant tissues was reduced in both the smDC and regDC groups. Foxp3 expression in peripheral blood CD4 T cells of the smDC group increased to 5.38% and that of the regDC group also rose to 3.87%. Moreover, the inflammatory infiltration in the tissues receiving transplanted hepatocytes was more obvious.
smDCs and regDCs were similar tolerogenic dendritic cells. They both could alleviate the immune injury by inducing CD4CD25Foxp3 regulatory T cells through the medium expression of MHC-II, CD40, CD80, and CD86 and the appropriate secretion of cytokines. Hepatocytes differentiated from ESCs displayed low immunogenicity.
本研究旨在探讨经小鼠胚胎干细胞（ESC）分化的肝细胞移植后半成熟树突状细胞（smDC）和调节性树突状细胞（regDC）诱导的耐受机制，并证实来源于 ESC 的肝细胞的低免疫原性。
培养绿色荧光蛋白标记的 129 只小鼠来源的 ESC 以分化为肝细胞。体外培养 smDC 和 regDC。从 129 只小鼠的肝脏中提取肝细胞后进行培养。在提前 3 天注射 smDC 或 regDC 后，分别将这些分化的肝细胞和正常肝细胞移植到 BALB/c 小鼠的肝脏中。随后，检查移植组织中的组织病理学特征和细胞因子，以及受体外周血 CD4 T 细胞中 Foxp3 的表达。
smDC 和 regDC 的形态表型相似。它们均表达中等水平的 MHC-II、CD40、CD80 和 CD86，高水平的 TGF-β和 IL-10，以及低水平的 IL-2。分化肝细胞的存活率延长，移植组织中的炎症浸润减少，在 smDC 和 regDC 组中均观察到这一现象。smDC 组外周血 CD4 T 细胞中 Foxp3 的表达增加到 5.38%，regDC 组也增加到 3.87%。此外，接受移植肝细胞的组织中的炎症浸润更为明显。
smDC 和 regDC 是类似的耐受原性树突状细胞。它们都可以通过中等水平表达 MHC-II、CD40、CD80 和 CD86 以及适当分泌细胞因子来诱导 CD4CD25Foxp3 调节性 T 细胞，从而减轻免疫损伤。来源于 ESC 的肝细胞具有低免疫原性。
