Mesenchymal stem cells support hepatocyte function in engineered liver grafts

Yoshie Kadota, Hiroshi Yagi, Kenta Inomata, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Minoru Kitago, Masahiro Shinoda, Hideaki Obara, Osamu Itano, Yuko Kitagawa

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology. In this context, the use of mesenchymal stem cells (MSC ) is an option meeting the criteria for therapeutic organ engineering. Ideally, supportive cells are required to (1) reduce the hepatic cell mass needed in an engineered liver by enhancing hepatocyte function, (2) modulate hepatic regeneration in a paracrine fashion or by direct contact, and (3) enhance the preservability of parenchymal cells during storage. Here, we describe enhanced hepatic function achieved using a strategy of sequential infusion of cells and illustrate the advantages of co-cultivating bone marrow-derived MSC s with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSC s and hepatocytes were transplanted into live animals. After blood flow was established, we show that expression of adhesion molecules and proangiogenic factors was upregulated in the graft.

Original languageEnglish
Pages (from-to)268-277
Number of pages10
JournalOrganogenesis
Volume10
Issue number2
DOIs
Publication statusPublished - 2014 Apr 1

Keywords

  • Cell transplantation
  • Organ transplantation
  • Regenerative medicine
  • Scaffold matrix
  • Stem cell
  • Tissue engineering

ASJC Scopus subject areas

  • Biomedical Engineering
  • Embryology
  • Developmental Biology
  • Transplantation

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