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Mesenchymal progenitor cells in mouse foetal liver regulate differentiation and proliferation of hepatoblasts
Author(s) -
Ito Keiichi,
Yanagida Ayaka,
Okada Ken,
Yamazaki Yuji,
Nakauchi Hiromitsu,
Kamiya Akihide
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12387
Subject(s) - mesenchymal stem cell , biology , microbiology and biotechnology , progenitor cell , stem cell , cellular differentiation , immunology , biochemistry , gene
Background & Aims 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 CD 45 − Ter119 − CD 71 − Dlk1 mid PDGFR α + 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 PDGFR α + 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.