Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells.
In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated "Advanced medical technology B" for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies.
1 Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine , Yamaguchi, Japan .
Shuji
S
Terai
Taro
T
Takami
Naoki
N
Yamamoto
Koichi
K
Fujisawa
Tsuyoshi
T
Ishikawa
Yohei
Y
Urata
Haruko
H
Tanimoto
Takuya
T
Iwamoto
Yuko
Y
Mizunaga
Takashi
T
Matsuda
Takashi
T
Oono
Miho
M
Marumoto
Guzel
G
Burganova
Luiz
L
Fernando Quintanilha
Isao
I
Hidaka
Yoshio
Y
Marumoto
Issei
I
Saeki
Koichi
K
Uchida
Takahiro
T
Yamasaki
Kenji
K
Tani
Yasuho
Y
Taura
Yasuhiko
Y
Fujii
Hiroshi
H
Nishina
Kiwamu
K
Okita
Isao
I
Sakaida
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000639:trends*; D002454:Cell Differentiation; D005544:Forecasting; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology* / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation / Q000639:trends*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D023822:Tissue Engineering / Q000639:trends