Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients

Abstract

Abstract.We have developed an in vivo mouse model [the green fluorescent protein (GFP) / carbon tetrachloride (CCl 4 ) model] and reported that infused GFP-positive bone marrow cells administered via a tail vein efficiently repopulated cirrhotic liver tissue under conditions of persistent liver damage induced by CCl 4 . Moreover, bone marrow cells infused into the liver improved liver function and ameliorated liver fibrosis with higher expression of matrix metalloproteinase 9 (MMP-9), consistent with improved survival rate. Based on these findings, we started a multicenter clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhosis patients and demonstrated the efficacy of this approach without unexpected complications. However, this 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 new liver regeneration therapy in which cells having a curative effect 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 subject. Herein, we present results for the GFP/CCl 4 model and ABMi therapy and future prospects for a new liver regeneration therapy.

Systematic review: the effects of autologous stem cell therapy for patients with liver disease

“…The majority of the published studies use HSCs of which 10 used the peripheral route, five the portal vein and nine the hepatic artery . One compared administration into the portal vein and peripherally and two between the hepatic artery and portal vein .…”

“…Largely, the published literature to date is designed to investigate safety and feasibility as the primary outcome measure. Seventeen of the twenty‐five studies which looked at liver function tests as an outcome measure did report statistically significant improvements in patients' results after cell therapy …”

“…Generally, very few studies look at patient‐important outcomes. Five and four studies respectively reported subsequent statistically significant changes in the prognostic Childs and MELD liver scores (Table ). Four studies reported significantly less clinical events, such as the worsening of ascites, seen in the follow‐up period of treated patients .…”

“…Four studies reported significantly less clinical events, such as the worsening of ascites, seen in the follow‐up period of treated patients . Of the studies which demonstrated benefit, three had been administered via the portal vein, five via the hepatic artery, six peripherally, one intradermally and in one, the route was unclear …”

Beneficial Effects ofOcimum gratissimumAqueous Extract on Rats with CCl4-Induced Acute Liver Injury

“…MMP9 is a member of the MMP protein family and plays a crucial role in various hepatic disorders [25], including inflammatory processes [26], fibrogenesis [27], and cancers [28, 29]. A variety of studies have indicated that CCl 4 could induce hepatic injury via elevating MMP9 protein level and activity [30–33].…”