Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 115, Issue 3, Pages 274-278Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.10R13FM
Keywords
liver cirrhosis; bone marrow; stem cell; liver regeneration; autologous bone marrow cell infusion (ABMi) therapy; liver disease
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Funding
- Japan Society for the Promotion of Science
- Ministry of Health, Labour, and Welfare
- Knowledge Cluster Initiative
- Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [22390150] Funding Source: KAKEN
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We have developed an in vivo mouse model [the green fluorescent protein (GFP) /carbon tetrachloride (CCl4) model] and reported that infused G FP-positive bone marrow cells administered via a tail vein efficiently repopulated cirrhotic liver tissue under conditions of persistent liver damage induced by CCl4. 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/CCl4 model and ABMi therapy and future prospects for a new liver regeneration therapy.
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