RESUMO
Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1a1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In this study, the Gunn rat was used as an animal model for heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the liver for up to 2 months. The transplanted iMSCs differentiated into functional hepatocytes as evidenced by partially suppressed hyperbilirubinemia and expression of multiple human-specific hepatocyte markers such as albumin, hepatocyte nuclear factor 4α, UGT1A1, cytokeratin 18, bile salt export pump, multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide, and α-fetoprotein. These findings imply that transplanted human iMSCs can contribute to liver regeneration in vivo and thus represent a promising tool for the treatment of inherited liver diseases.
Assuntos
Hepatopatias/terapia , Regeneração Hepática , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Pluripotentes/citologia , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Albuminas/genética , Albuminas/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Queratina-18/genética , Queratina-18/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Células-Tronco Pluripotentes/metabolismo , Ratos , Ratos Gunn , Simportadores/genética , Simportadores/metabolismoRESUMO
Human epicardium-derived cells (EPDC) were reprogrammed to generate two iPSC lines, MCDU1i-EPDC and MCDU2i-EPDC, by nucleofection of episomal-based plasmids expressing the reprogramming factors OCT4, SOX2, KLF4, c-MYC, NANOG and LIN28. Pluripotency was confirmed in vitro by immunofluorescence analysis and embryoid body formation. The iPSC lines and the human embryonic stem cell line H1 show a Pearson correlation co-efficient of 0.951 (MCDU1i-EPDC) and 0.937 (MCDU2i-EPDC) as assessed by comparative transcriptome profiling.
