Jaymie Siqi Lin1,2, Lei Zhou1, Antony Sagayaraj1, Nur Halisah Bte Jumat1, Mahesh Choolani3, Jerry Kok Yen Chan4,5, Arijit Biswas3, Peng Cheang Wong3, Seng Gee Lim1, Yock Young Dan1,6. 1. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2. Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 4. Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore. 5. Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore. 6. Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore.
Abstract
BACKGROUND AND AIM: Human amniotic epithelial cells (hAECs) have been touted as an ideal stem cell candidate, being ethically neutral, immunologically naïve, plentiful in origin, and retaining plasticity in its fetal stage. We hypothesized that by applying natural physiological signals of the developing liver, hAECs can be coaxed into becoming functional immunopermissive hepatocyte-like cells. These cells would have tremendous potential for allogenic cellular transplantation in the treatment of chronic liver insufficiency. METHODS: hAECs were obtained from term placentas and subjected to hepatic trans-differentiation. Hepatic differentiated cells were analyzed with immunophenotyping, electron microscopy, reverse transcription-polymerase chain reaction as well as characterized for hepatic metabolic function. In vivo efficacy was tested using intrasplenic transplantation into non-obese diabetic (NOD) Scid Gamma mice with thioacetamide-induced chronic liver failure and analyzed for engraftment and improvement in liver indices. RESULTS: With hepatic differentiation, hAECs assumed a hepatocytic polygonal morphology with upregulation of transcription factors responsible for liver specification. These hepatic differentiated-hAECs (HD-AECs) demonstrated bile canaliculi formation, secreted albumin, eliminated indo-cyanine green, uptook low-density lipoprotein, and inducible CYP3A4 and CYP2C9 enzymatic activities. Transplantation of HD-AECs and de novo hAECs in mice model of cirrhosis showed successful in vivo engraftment and differentiation into functional hepatocytes positive for human-specific albumin. HD-AEC cells that had undergone hepatic differentiation showed the greatest improvement in albumin function while preserving human leukocyte antigen-G expression postdifferentiation. CONCLUSION: hAECs were able to differentiate into functional hepatocyte-like cells both in vivo and in vitro. They showed therapeutic efficacy after transplantation in mice model of cirrhosis, offering an exciting source of cells for generation of functionally useful hepatocytes.
BACKGROUND AND AIM: Human amniotic epithelial cells (hAECs) have been touted as an ideal stem cell candidate, being ethically neutral, immunologically naïve, plentiful in origin, and retaining plasticity in its fetal stage. We hypothesized that by applying natural physiological signals of the developing liver, hAECs can be coaxed into becoming functional immunopermissive hepatocyte-like cells. These cells would have tremendous potential for allogenic cellular transplantation in the treatment of chronic liver insufficiency. METHODS: hAECs were obtained from term placentas and subjected to hepatic trans-differentiation. Hepatic differentiated cells were analyzed with immunophenotyping, electron microscopy, reverse transcription-polymerase chain reaction as well as characterized for hepatic metabolic function. In vivo efficacy was tested using intrasplenic transplantation into non-obese diabetic (NOD) Scid Gamma mice with thioacetamide-induced chronic liver failure and analyzed for engraftment and improvement in liver indices. RESULTS: With hepatic differentiation, hAECs assumed a hepatocytic polygonal morphology with upregulation of transcription factors responsible for liver specification. These hepatic differentiated-hAECs (HD-AECs) demonstrated bile canaliculi formation, secreted albumin, eliminated indo-cyanine green, uptook low-density lipoprotein, and inducible CYP3A4 and CYP2C9 enzymatic activities. Transplantation of HD-AECs and de novo hAECs in mice model of cirrhosis showed successful in vivo engraftment and differentiation into functional hepatocytes positive for human-specific albumin. HD-AEC cells that had undergone hepatic differentiation showed the greatest improvement in albumin function while preserving human leukocyte antigen-G expression postdifferentiation. CONCLUSION: hAECs were able to differentiate into functional hepatocyte-like cells both in vivo and in vitro. They showed therapeutic efficacy after transplantation in mice model of cirrhosis, offering an exciting source of cells for generation of functionally useful hepatocytes.
Authors: Salomon Poliwoda; Nazir Noor; Evan Downs; Amanda Schaaf; Abigail Cantwell; Latha Ganti; Alan D Kaye; Luke I Mosel; Caroline B Carroll; Omar Viswanath; Ivan Urits Journal: Orthop Rev (Pavia) Date: 2022-08-25
Authors: Julieta L Maymó; Rodrigo Riedel; Antonio Pérez-Pérez; Marta Magatti; Bernardo Maskin; José Luis Dueñas; Ornella Parolini; Víctor Sánchez-Margalet; Cecilia L Varone Journal: PLoS One Date: 2018-01-18 Impact factor: 3.240