Mesenchymal progenitor cells in mouse foetal liver regulate differentiation and proliferation of hepatoblasts.
OBJECTIVE
Hepatoblasts are somatic progenitor cells of the foetal liver that possess high proliferative capacity and bi-potency for differentiation into both hepatocytes and cholangiocytes. Although mesenchymal cells are known to be important for liver ontogeny, current understanding of their interaction with hepatoblasts remains obscure. Mesenchymal cell populations in the developing liver were purified and their potential to support proliferation and differentiation of hepatoblasts was examined.


METHODS
Foetal liver cells were fractionated with a flow cytometer using antibodies against cell surface markers. Gene expression of mesenchymal-specific transcripts and morphological characteristics were analysed. The ability of the mesenchymal cells to support hepatoblast function was analysed using a transwell and direct coculture system.


RESULTS
CD45(-) Ter119(-) CD71(-) Dlk1(mid) PDGFRα(+) cells from the mid-foetal stage liver expressed the mesenchymal cell-specific transcription factors H2.0-like homeobox 1 and LIM homeobox 2 at high levels. Foetal mesenchymal cells make contact with hepatoblasts in vivo and possess the potential to differentiate into chondrocytes, osteocytes and adipocytes under appropriate cell culture conditions, indicating that these cells are possible candidates for mesenchymal stem/progenitor cells. Foetal mesenchymal cells expressed pleiotrophin, hepatocyte growth factor and midkine 1, which are involved in the growth of hepatoblasts. Using the coculture system with hepatoblasts and foetal mesenchymal cells, these cells were shown to support proliferation and maturation of hepatoblasts through indirect and direct interactions respectively.


CONCLUSIONS
Dlk1(mid) PDGFRα(+) cells in non-haematopoetic fraction derived from the foetal liver exhibit mesenchymal stem/progenitor cell characteristics and have abilities to support proliferation and differentiation of hepatoblasts.
Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Keiichi
K
Ito
Ayaka
A
Yanagida
Ken
K
Okada
Yuji
Y
Yamazaki
Hiromitsu
H
Nakauchi
Akihide
A
Kamiya
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005333:Fetus / Q000166:cytology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins; D022781:Hepatocytes / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D049452:Green Fluorescent Proteins
cell-cell interaction; hepatoblast; liver development; mesenchymal stem/progenitor cell