Clinical and experimental pancreatic islet transplantation to striated muscle: establishment of a vascular system similar to that in native islets.
Clinical and experimental pancreatic islet transplantation to striated muscle: establishment of a vascular system similar to that in native islets.
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DOI：
10.2337/db10-0205
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发表时间：
2010-10
期刊：
影响因子：
7.7
通讯作者：
Phillipson M
中科院分区：
文献类型：
--
作者：
Christoffersson G;Henriksnäs J;Johansson L;Rolny C;Ahlström H;Caballero-Corbalan J;Segersvärd R;Permert J;Korsgren O;Carlsson PO;Phillipson M
通过将胰岛移植到肝脏中来治愈1型糖尿病与不良的长期结局和移植失败相关，至少部分原因是移植物血运重建不足。本研究的目的是评估横纹肌作为胰岛移植的潜在血管生成部位。目前的研究提出了一个新的实验模型，发现适用于临床胰岛移植。胰岛被植入横纹肌和胰岛内血管密度和血流可视化活体和共聚焦显微镜在小鼠和三个自体移植胰腺切除患者的磁共振成像。通过重复注射Gr-1抗体使小鼠出现糖尿病，并通过四氧嘧啶治疗诱导糖尿病。与肝脏移植的胰岛相反，移植到小鼠肌肉中的胰岛的血管密度和血流完全与完整胰腺内的胰岛相当。在肌肉部位的胰岛血管再生的启动依赖于中性粒细胞，并且通过治愈糖尿病小鼠证实了移植到肌肉的胰岛的功能。实验数据在自体移植患者中得到证实，通过高分辨率磁共振成像，与邻近肌肉组织相比，在前臂肌肉中移植的胰岛中测量到更高的血浆体积。这项研究提出了一种新的模式，在胰岛移植，其中招募的中性粒细胞是至关重要的功能恢复胰岛内血液灌注移植到横纹肌下的实验和临床情况。
Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation. The current study presents a new experimental model that is found to be applicable to clinical islet transplantation. Islets were implanted into striated muscle and intraislet vascular density and blood flow were visualized with intravital and confocal microscopy in mice and by magnetic resonance imaging in three autotransplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody, and diabetes was induced by alloxan treatment. Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable with those of islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in autotransplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared with adjacent muscle tissue through high-resolution magnetic resonance imaging. This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intraislet blood perfusion following transplantation to striated muscle under experimental and clinical situations.
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影响因子：
7.7
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作者：
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作者：
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