Improving islet transplantation by gene delivery of hepatocyte growth factor (HGF) and its downstream target, protein kinase B (PKB)/Akt
Improving islet transplantation by gene delivery of hepatocyte growth factor (HGF) and its downstream target, protein kinase B (PKB)/Akt
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DOI：
10.1007/s12013-007-0024-7
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Garcia-Ocana, Adolfo
中科院分区：
文献类型：
--
作者：
Fiaschi-Taesch, Nathalie;Stewart, Andrew F.;Garcia-Ocana, Adolfo
临床研究表明，胰岛移植可能是一种有用的程序，以取代β细胞功能的患者1型糖尿病。胰岛移植面临许多挑战，包括手术本身的并发症，免疫抑制方案的毒性，以及胰岛功能和胰岛素独立性随时间的丧失。尽管目前取得了成功，但仍存在挑战，这些研究指出，胰岛组织的巨大稀缺性阻碍了在临床环境中更大规模地使用胰岛移植。为了解决这个问题，许多研究小组正试图确定不同的胰岛生长因子和细胞内分子，这些因子和细胞内分子能够改善胰岛移植物的存活和功能，从而减少成功移植所需的胰岛数量。在这些生长因子中，肝细胞生长因子（HGF）是一种已知可以改善多种器官/细胞移植的因子，在四种不同的胰岛移植啮齿动物模型中，它在提高胰岛移植存活率和减少成功移植所需的胰岛数量方面显示出了令人鼓舞的结果。蛋白激酶B (PKB)/Akt是一种促生存的细胞内信号分子，已知在β细胞中被几种不同的生长因子（包括HGF）激活。在糖尿病SCID小鼠胰岛移植的最小胰岛质量模型中，PKB/Akt也显示出改善人类胰岛移植物存活和功能的有希望的结果。增加我们对HGF、PKB/Akt和其他新兴分子如何改善胰岛移植的了解，可能为未来的治疗方法提供基础，旨在增加β细胞功能可以成功替代的患者数量。
Clinical studies have demonstrated that islet transplantation may be a useful procedure to replace beta cell function in patients with Type I diabetes. Islet transplantation faces many challenges, including complications associated with the procedure itself, the toxicity of immunosuppression regimens, and to the loss of islet function and insulin-independence with time. Despite the current successes, and residual challenges, these studies have pointed out an enormous scarcity of islet tissue that precludes the use of islet transplantation in a clinical setting on a wider scale. To address this problem, many research groups are trying to identify different islet growth factors and intracellular molecules capable of improving islet graft survival and function, therefore reducing the number of islets needed for successful transplantation. Among these growth factors, hepatocyte growth factor (HGF), a factor known to improve transplantation of a variety of organs/cells, has shown promising results in increasing islet graft survival and reducing the number of islets needed for successful transplantation in four different rodent models of islet transplantation. Protein kinase B (PKB)/Akt, a pro-survival intracellular signaling molecule is known to be activated in the beta cell by several different growth factors, including HGF. PKB/Akt has also shown promising results for improving human islet graft survival and function in a minimal islet mass model of islet transplantation in diabetic SCID mice. Increasing our knowledge on how HGF, PKB/Akt and other emerging molecules work for improving islet transplantation may provide substrate for future therapeutic approaches aimed at increasing the number of patients in which beta cell function can be successfully replaced.