Treatment of alpha-1 antitrypsin deficiency using hepatic-specified cells derived from human-induced pluripotent stem cells

Authors: Chen Y; Li, R; Zhang, L; Gan, L; Ding, J.

Affiliations: Guizhou Med Univ, Affiliated Hosp 3, Dept Infect Dis, 7 Qixing Rd, Duyun 558000, Guizhou, Peoples R China; Chongqing Univ Cent Hosp, Chongqing Emergency Med Ctr, Dept Gen Med, Chongqing, Peoples R China.

Publication: American Journal of Translational Research; 2021; 13. 2710–2716. June 2021

Abstract: OBJECTIVE: alpha-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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.