Differentiation of mesenchymal stromal cells derived from umbilical cord Wharton's jelly into hepatocyte-like cells.

Background Aims: Mesenchymal stromal cells (MSC) isolated from bone marrow (BM), adipose tissue and umbilical cord blood can be induced to differentiate into hepatocyte-like cells. MSC can also be isolated from umbilical cord Wharton's jelly (UC MSC), which can be easily obtained. UC MSC are more primitive MSC than those isolated from other tissue sources and do not express the major histocompatibility complex (MHC) class II (HLA-DR) antigens. Previous studies have shown that UC MSC are still viable and not rejected 4 months after transplantation as xenografts, without the need for immune suppression, suggesting that they are a favorable cell source for transplantation.

Methods: UC MSC were induced to differentiate into hepatocyte-like cells by a simple one-step protocol with hepatotic growth factor (HGF) and fibroblast growth factor-4 (FGF-4). Differentiated cells were examined for the expression of hepatocyte-specific markers and hepatocyte functions.

Results: UC MSC were isolated. Flow cytometry analysis showed that they expressed the MSC-specific markers. They differentiated into osteoblast-, adipocyte- and chondrocyte-like cells, showing their multipotent differentiation potential. Immunocytochemistry, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis demonstrated that UC MSC expressed the hepatocyte-specific markers albumin (ALB), human alpha-fetoprotein (AFP) and cytokeratin 18 (CK-18) following hepatocyte induction. Periodic acid-Schiff staining showed that differentiated UC MSC could store glycogen, and an low-density lipoprotein (LDL)-uptake assay showed that they could uptake LDL.

Conclusions: This study demonstrates that UC MSC can differentiate into functional hepatocyte-like cells following the induction of HGF and FGF-4. UC MSC can serve as a favorable cell source for tissue engineering in the treatment of liver disease.