Liver tissue engineering utilizing hepatocytes propagated in mouse livers in vivo.
Recent advances in tissue engineering technologies have highlighted the ability to create functional liver systems using isolated hepatocytes in vivo. Considering the serious shortage of donor livers that can be used for hepatocyte isolation, it has remained imperative to establish  a hepatocyte propagation protocol to provide highly efficient cell recovery allowing for subsequent tissue engineering procedures. Donor primary hepatocytes were isolated from human α-1 antitrypsin (hA1AT) transgenic mice and were transplanted into the recipient liver of urokinase-type  plasminogen activator-severe combined immunodeficiency (uPA/SCID) mice. Transplanted donor hepatocytes actively proliferated within the recipient liver of the uPA/SCID mice. At week 8 or later, full repopulation of the uPA/SCID livers with the transplanted hA1AT hepatocytes were confirmed  by blood examination and histological assessment. Proliferated hA1AT hepatocytes were recovered from the recipient uPA/SCID mice, and we generated hepatocyte sheets using these recovered hepatocytes for subsequent transplantation into the subcutaneous space of mice. Stable persistency of the  subcutaneously engineered liver tissues was confirmed for up to 90 days, which was the length of our present study. These new data demonstrate the feasibility in propagating murine hepatocytes prior to the development of hepatic cells and bioengineered liver systems. The ability to regenerate  and expand hepatocytes has potential clinical value whereby procurement of small amounts of tissue could be expanded to sufficient quantities prior to their use in hepatocyte transplantation or other hepatocyte-based therapies.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. ohashi@abmes.twmu.ac.jp
Kazuo
K
Ohashi
Kohei
K
Tatsumi
Chise
C
Tateno
Miho
M
Kataoka
Rie
R
Utoh
Katsutoshi
K
Yoshizato
Teruo
T
Okano
D000178:Acrylamides / Q000737:chemistry; D000180:Acrylic Resins; D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D049109:Cell Proliferation; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D011108:Polymers / Q000737:chemistry; D044968:Regenerative Medicine; D023822:Tissue Engineering; D014183:Transplantation, Heterologous; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000178:Acrylamides; D000180:Acrylic Resins; D011108:Polymers; D000515:alpha 1-Antitrypsin; C052970:poly-N-isopropylacrylamide