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Adult stem cells that reside in adult tissues have been deemed to possess great potential for clinical application because of their capabilities of self-renewal and differentiation. However, the limitations such as infection risks and low isolation rate make the search for appropriate source to be continued. Here, we demonstrate isolation of progenitors from human foreskin tissue samples, which have fibroblast-like morphology and could be easily propagated for more than 50 passages. These foreskin-derived fibroblast-like stromal cells (FDSCs) expressed CD90, CD105, CD166, CD73, SH3, and SH4, which is similar to the immunophenotypes of human bone marrow-derived mesenchymal stem cells. In comparison with Hs68, the human fibroblast cell line, FDSCs are positive for CD105 and absent for CD54 expression. Further, FDSCs could be induced to differentiate into osteocytes, adipocytes, neural cells, smooth muscle cells, Schwann-like cells, and hepatocyte-like cells. Interestingly, when cultured in Dulbecco's modified Eagle's medium/F12 medium, FDSCs can form spheres with increased expression levels of fibronectin and vimentin. In conclusion, foreskin can serve as a valuable source of multipotent cells with the capabilities for endodermal, mesodermal, and ectodermal cells. Coupled with the advantages of their easy access, isolation, and propagation, these foreskin-derived stromal cells might be of potential use in future studies in stem cell differentiation and therapeutic application.

Foreskin fibroblast-like stromal cells (FDSCs) are progenitors isolated from human tissue that can differentiate into diverse cell types. Many types of stem cells can differentiate into hepatocyte-like cells, which could be used for drug testing or in liver regeneration therapy, but whether FDSCs can be converted into functional hepatocytes is unknown. FDSCs show divergent properties when cultured in distinct media, forming spheres in Dulbecco's modified Eagle's medium (DMEM) containing F12, epidermal growth factor (EGF), and basic fibroblast growth factor (b-FGF), but have fibroblast-like morphology when cultured in DMEM-based growth medium. Both cell populations express the typical mesenchymal stem cell markers CD90, CD105, and CD73, but the p75 neurotrophin receptor (p75NTR) was detected only in FDSC spheres. Both types of FDSCs can differentiate into hepatocyte-like cells, which express typical liver markers, including albumin and hepatocyte paraffin 1 (Hep Par1), along with liver-specific biological activities. When plasmids containing the human hepatitis B virus (HBV) genome were transfected transiently into FDSCs, differentiated hepatocyte-like cells secrete large amounts of HBe and HBs antigens. FDSCs could be used for clinical hepatic therapy and/or serve as a model of HBV. [ABSTRACT FROM AUTHOR]