Autologous macrophage therapy promotes stem cell-mediated liver regeneration:a novel therapy for end-stage liver disease

自体巨噬细胞治疗促进干细胞介导的肝再生：终末期肝病的新疗法

• 批准号: G1000868/1
• 负责人: Stuart Forbes
• 金额: $ 93.17万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000868%2F1
• 关键词: Autologous; macrophage; therapy; promotes; stem

Liver disease is the 5th commonest cause of death in the UK and deaths from cirrhosis are rapidly rising. Currently the only curative option for end-stage liver disease is liver transplantation and this is limited in availability due to a lack of suitable donor livers. As a result of this, many patients die whilst waiting for a donor organ, hence new therapeutic strategies for patients with end-stage liver disease are urgently required. Cell therapy using bone marrow has been tested in rodents and has shown to significantly reduce liver scarring, which is a precursor to cirrhosis. We have found that in addition this effect bone marrow therapy stimulates the livers own stem cells to start dividing and regenerate the liver. We have identified the cell type within the bone marrow that is responsible for this effect termed macrophages. This is exciting as these cells can be isolated from a patient?s blood in an immature form in large numbers and matured in the laboratory effectively. Here, we describe a novel approach to the treatment of liver cirrhosis using blood derived cells which have been matured outwith the body into macrophages prior to re-injection into the blood stream. This therapy is simple to administer and has the potential to reduce liver scarring and promote liver regeneration. The pre-clinical studies are designed to test the safety and effectiveness of this technique in a wide range of liver disease models- if they are effective they will be directly translated into patients in a clinical pilot study.

肝病是英国第五大常见死因，肝硬化死亡人数正在迅速上升。目前，终末期肝病的唯一治疗选择是肝移植，由于缺乏合适的供体肝脏，这是有限的。因此，许多患者在等待供体器官时死亡，因此迫切需要针对终末期肝病患者的新治疗策略。使用骨髓的细胞疗法已在啮齿动物中进行了测试，并已显示出显着减少肝瘢痕形成，这是肝硬化的前兆。我们发现，除了这种效果，骨髓疗法还刺激肝脏自身的干细胞开始分裂并再生肝脏。我们已经确定了骨髓中负责这种效应的细胞类型，称为巨噬细胞。这是令人兴奋的，因为这些细胞可以从病人身上分离出来。在实验室中，我们成功地将人的血液以不成熟的形式大量地成熟。在这里，我们描述了一种新的方法来治疗肝硬化，使用血液来源的细胞，这些细胞在重新注射到血流中之前已经在体内成熟为巨噬细胞。这种疗法易于管理，并有可能减少肝脏瘢痕形成和促进肝脏再生。临床前研究旨在测试该技术在广泛的肝病模型中的安全性和有效性-如果有效，则将直接转化为临床试点研究中的患者。