Mesenchymal stem cells support hepatocyte function in engineered liver grafts.
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 MSCs with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSCs 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.
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Yoshie
Y
Kadota
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Hiroshi
H
Yagi
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Kenta
K
Inomata
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Kentaro
K
Matsubara
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Taizo
T
Hibi
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Yuta
Y
Abe
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Minoru
M
Kitago
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Masahiro
M
Shinoda
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Hideaki
H
Obara
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Osamu
O
Itano
Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.
Yuko
Y
Kitagawa
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D008099:Liver / Q000502:physiology*; D016031:Liver Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
D043925:Angiogenesis Inducing Agents; D015815:Cell Adhesion Molecules
cell transplantation; organ transplantation; regenerative medicine; scaffold matrix; stem cell; tissue engineering