FIG. 5.

Transplanted human iMSCs successfully engrafted in Gunn rat liver and expressed hepatocyte markers. Gunn rat liver tissue and serum were analyzed 2 months after iMSC transplantation. (A) The presence of human ALB transcripts within Gunn rat liver was analyzed by qPCR. Additional hepatocyte-associated genes such as (B) UGT1A1, (C) HNF4α, (D) BSEP, (E) NTCP, (F) MRP2, (G) CYP1A2, (H) CYP2D6/7, (I) CYP3A4/5/7, and (J) AFP were found by human-specific primers for qPCR. The results were normalized to human liver samples, which were set to 100%. Thus, the bars represent proportions of the expression values of human liver. (K) Human-specific primers for HPRT1 were used to assess the total abundance of human cells derived from iMSCs. (L) The MSC marker CD105 remained detectable by human-specific primers in qPCR within the host Gunn rat livers. (M) Human RANTES and SERPINE1 were detected by protein arrays in the serum of Gunn rats transplanted with human iMSCs. A representative blot of the control and one transplantation group is shown. The three spot pairs in the corners represent protein array quality controls. Densitometric analysis of (N) RANTES and (O) SERPINE1 spots (highlighted by red boxes). The small bar of the control group represents the background pixel density (pixel density in % to the control spots). (A–I, K–L: control n = 4, ESC-iMSC, passage 10, n = 3; iPSC-iMSC, passage 10, n = 3, groups without significant differences share similar letters; P < 0.05). AFP, α-fetoprotein; BSEP, bile salt export pump; HNF4α, hepatocyte nuclear factor 4α; MRP2, multidrug resistance protein 2; NTCP, Na/taurocholate-cotransporting polypeptide; qPCR, quantitative real-time polymerase chain reaction; Ugt1A1, uridine diphosphate glucuronosyltransferase-1a1.