Our regeneration therapies using autologous bone marrow cells for liver cirrhosis

In our animal studies, we have reported that bone marrow cells (BMCs) infused via a peripheral vein efficiently repopulated cirrhotic liver. Repopulated BMCs were seen to produce collegenases including MMP-9. As a result, reduced liver fibrosis, elevation in serum albumin levels, and significant increase in survival rate were confirmed. Based on these evidences, we have started "Autologous bone marrow cell infusion (ABMi) therapy" using non-cultured autologous whole BMCs. This therapy was officially approved as "Advanced medical technology B" in Japan. However, ABMi therapy involves bone marrow (BM) aspiration under general anesthesia. We therefore developed a less-invasive liver regeneration therapy using cultured autologous mesenchymal stem cells (MSCs) isolated from a small amount of BM fluid aspirated under local anesthesia. We revealed that the peripheral infusion of cultured human BMCs reduced hepatic fibrosis in the immunodeficient cirrhotic mice, consistent with the maintaining redox homeostasis in hepatic stellate cells and hepatocytes. Moreover, supplementation of MSC's exosomes reduced the levels of ROS form cultured hepatocytes. To evaluate safety by using canine models, cultured autologous MSCs were administered to the same subject in approximately 3 times the quantities and at 10 times the concentration used in humans. And then, we constructed the cell-processing facility with new isolator system to confer protection from hepatitis virus. Here, we present the current status and prospects for our liver regeneration therapies.