Taro Takami, Shuji Terai, Isao Sakaida
Yamaguchi University, Japan
Taro Takami is a Senior Assistant Professor at Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan . Recent research projects include cell therapy for neurogenic bladder and prostate cancer. He is a is an Associate Faculty Member who works with Faculty Member Isao Sakaida to recommend the scientific literature in their field.
We have developed autologous bone marrow cell infusion (ABMi) therapy, which was a method of liver regeneration for liver cirrhotic patients using non-cultured autologous whole bone marrow cells, and reported the efficacy and safety of this approach. We recently also confirmed that frequent BMC infusion contributed to suppressed tumor initiation during stages of hepatocarcinogenesis through the stabilization of redox homeostasis in hepatocarcinogenic mice with liver cirrhosis. On the other hand, our ABMi therapy involves bone marrow aspiration under general anesthesia, and is not indicated for patients for whom general anesthesia is difficult. We therefore aimed to develop a less-invasive liver regeneration therapy in which cells having curative effect(s) on liver cirrhosis are isolated and cultured from a small amount of autologous bone marrow aspirated under local anesthesia and infused back into the same patient, showing that the indications would be able to be expanded, as collection of bone marrow fluid would no longer need to be performed under general anesthesia. We revealed that the infusion of cultured human bone marrow derived CD73/CD90/CD105 positive and CD45 negative cells with fetal bovine serum (FBS)-containing D-MEM medium, which were having mesenchymal characteristics, reduced hepatic fibrosis in the immunodeficient NOD-SCID cirrhotic mice, consistent with the reduced oxidative stress in human stellate cells co-cultured with human mesenchymal stem cells in vitro. For the clinical trial using cultured bone marrow mesenchymal stem cells, we are now preparing safety evaluation guidelines and a system conforming to Standard Operating Procedure (SOP) at a Good Manufacturing Practice (GMP)-grade cellprocessing center in our university hospital. Here, we present the current status and prospects for our liver regeneration therapy using autologous bone marrow-derived cells.