Chen Yingqiang, Li Ruoqing, Zhang Lin, Gan Linlin, Ding Jianqiang
Department of Infectious Diseases, The Third Affiliated Hospital of Guizhou Medical University Duyun, Guizhou Province, China.
Department of General Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center Chongqing, China.
Am J Transl Res. 2021 Apr 15;13(4):2710-2716. eCollection 2021.
α-1 antitrypsin deficiency (AATD) is an inherited liver disease characterized by the "Z" mutations, which can cause pulmonary emphysema and liver fibrosis. Transplantation of the organ (i.e., the lung/liver) is the best treatment method, however, the scarcity of suitable donors limits its application. The cell transplantation technique poses an alternative way of combating liver failure.
Hepatic specific differentiation of the human induced pluripotent stem cells (iPSCs) was initiated with 100 ng/mL activin A, followed by 20 ng/mL of BMP-4 and 10 ng/mL of FGF-2. The cells were transplanted into the livers of AATD transgenic mice using intra-splenic injections. FK506 was used as an immunosuppressor. At 1, 3, and 6 months post-transplantation, the human serum albumin (HSA) levels and its DNA contents, and the mice serum and liver tissues were measured using enzyme-linked immunosorbent assays (ELISA), polymerase chain reactions (PCR), and immunohistochemistry to estimate the repopulation of the hepatic-specified cells.
Post transplantation, the hepatic-specified cells were found to be successfully and progressively repopulated in the transgenic mice livers. Additionally, the hepatic-specified cells did not display any carcinogenicity, as confirmed by the absence of any tumors on the animals.
We provide a time saving and low cost method of transplanting hepatic-specified cells into the livers of AATD mice without any risk of carcinogenicity, a method that may be a potential option for the treatment of AATD.
α-1抗胰蛋白酶缺乏症（AATD）是一种由“Z”突变引起的遗传性肝病，可导致肺气肿和肝纤维化。器官移植（即肺/肝移植）是最佳治疗方法，然而，合适供体的稀缺限制了其应用。细胞移植技术为对抗肝衰竭提供了一种替代方法。
用100 ng/mL激活素A启动人诱导多能干细胞（iPSC）的肝特异性分化，随后加入20 ng/mL骨形态发生蛋白-4和10 ng/mL成纤维细胞生长因子-2。通过脾内注射将细胞移植到AATD转基因小鼠的肝脏中。使用FK506作为免疫抑制剂。在移植后1、3和6个月，使用酶联免疫吸附测定（ELISA）、聚合酶链反应（PCR）和免疫组织化学测量人血清白蛋白（HSA）水平及其DNA含量，以及小鼠血清和肝组织，以评估肝特异性细胞的再填充情况。
移植后，发现肝特异性细胞在转基因小鼠肝脏中成功且逐渐地再填充。此外，动物未出现任何肿瘤，证实肝特异性细胞未显示任何致癌性。
我们提供了一种省时且低成本的方法，将肝特异性细胞移植到AATD小鼠肝脏中且无任何致癌风险，该方法可能是治疗AATD的一种潜在选择。
