The Effect of liver regeneration on hESCs transplanted into SCID mice

ABSTRACT: A source of functioning hepatocytes for liver cell transplantation and liver support is in need. hESCs , when transplanted, generally form teratomas. We studied capacity of hESCs to differentiate to hepatocyte like cells under the effect of in vivo liver regeneration. In SCID-Beige mice hepatocyte replication peaked 48 hours after CCl4 injection; 24 hours earlier 106 hESCs or EBs at different stages of differentiation were transplanted into the spleen. Comparisons were made to teratomas formed in the hind limb of untreated animals. RT-PCR and gene microarray were used for liver and human specific markers. Immunohistochemistry to AFP,AAT, ALB, HEP-PAR I AND CK-18,19 were performed. EBs formed a single large teratoma in the spleen and small teratomas in the liver. Expression of PCR- identified liver specific markers was greater in the spleen than in the liver. Adult hepatocyte specific markers were expressed in the hind limb teratoma excised after 7 weeks. When late EBs were transplanted before CCl4 exposure, no teratomas formed. Rather, an abundance of probably undifferentiated ectodermal origin cells presented. In this descriptive study, transplanted early human EBs formed teratomas that differed in size and molecular markers. Within teratomas, the degree of maturation into hepatocytes correlated better with the time duration in vivo than with growth stimulation. Late EBs formed non differentiated ectodermal cells only in a regenerative microenvironment.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE31136 | GEO | 2011/12/31

SECONDARY ACCESSION(S): PRJNA144949

REPOSITORIES: GEO