Fibroblast growth factor 7 releasing particles enhance islet engraftment and improve metabolic control following islet transplantation in mice with diabetes.
Fibroblast growth factor 7 releasing particles enhance islet engraftment and improve metabolic control following islet transplantation in mice with diabetes.
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成纤维细胞生长因子 7 释放颗粒可增强糖尿病小鼠的胰岛移植并改善胰岛移植后的代谢控制。
DOI：
10.1111/ajt.16488
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Forbes S
中科院分区：
文献类型：
--
作者：
Alwahsh SM;Qutachi O;Starkey Lewis PJ;Bond A;Noble J;Burgoyne P;Morton N;Carter R;Mann J;Ferreira-Gonzalez S;Alvarez-Paino M;Forbes SJ;Shakesheff KM;Forbes S
1型糖尿病（T1 D）的胰岛移植受到胰岛植入肝脏不良的限制，每个受体需要两到三个供体胰腺。我们的目的是调节肝脏以增强胰岛植入，从而改善长期移植物功能。糖尿病小鼠接受非治愈性胰岛移植（n = 400个胰岛）通过肝门静脉（HPV）与载纤维母细胞生长因子7的半乳糖基化聚乙烯（DL-丙交酯-共-乙醇酸）（FGF 7-GAL-PLGA）颗粒; 26 µm直径颗粒特异性靶向肝脏，在短期实验中促进肝细胞增殖：在接受0.1 mg FGF 7-GAL-PLGA颗粒（60 ng FGF 7）与溶剂的小鼠中，特异性诱导肝脏中的细胞增殖，其有效性和特异性高于皮下FGF 7（1.25 mg/kg ×2剂量;约75 µg FGF 7）。移植后72小时，接受胰岛和FGF 7-GAL-PLGA颗粒的小鼠的肝切片中移植的胰岛和血管形成的数量大于仅接受胰岛的小鼠。更多接受胰岛和FGF 7-GAL-PLGA颗粒的小鼠（8只中的6只）在移植后30天使血糖浓度正常化，而8只单独接受胰岛的小鼠中的0只在此阶段没有证据表明肝脏内细胞增殖增加，肝功能测试正常。这项工作表明，肝脏靶向FGF 7-GAL-PLGA颗粒实现了选择性FGF 7递送至肝脏，促进胰岛移植，以帮助血糖水平正常化，并具有良好的安全性。将胰岛与负载成纤维细胞生长因子7的肝靶向生物可降解微粒共移植到糖尿病小鼠肝脏中，导致短期肝细胞增殖，并改善胰岛植入，与单独移植胰岛相比，具有上级长期血糖控制。参见第2927页的社论。
Transplantation of islets in type 1 diabetes (T1D) is limited by poor islet engraftment into the liver, with two to three donor pancreases required per recipient. We aimed to condition the liver to enhance islet engraftment to improve long‐term graft function. Diabetic mice received a non‐curative islet transplant (n = 400 islets) via the hepatic portal vein (HPV) with fibroblast growth factor 7‐loaded galactosylated poly(DL‐lactide‐co‐glycolic acid) (FGF7‐GAL‐PLGA) particles; 26‐µm diameter particles specifically targeted the liver, promoting hepatocyte proliferation in short‐term experiments: in mice receiving 0.1‐mg FGF7‐GAL‐PLGA particles (60‐ng FGF7) vs vehicle, cell proliferation was induced specifically in the liver with greater efficacy and specificity than subcutaneous FGF7 (1.25 mg/kg ×2 doses; ~75‐µg FGF7). Numbers of engrafted islets and vascularization were greater in liver sections of mice receiving islets and FGF7‐GAL‐PLGA particles vs mice receiving islets alone, 72 h posttransplant. More mice (six of eight) that received islets and FGF7‐GAL‐PLGA particles normalized blood glucose concentrations by 30‐days posttransplant, versus zero of eight mice receiving islets alone with no evidence of increased proliferation of cells within the liver at this stage and normal liver function tests. This work shows that liver‐targeted FGF7‐GAL‐PLGA particles achieve selective FGF7 delivery to the liver‐promoting islet engraftment to help normalize blood glucose levels with a good safety profile. Cotransplantation of islets with liver‐targeted, biodegradable microparticles loaded with fibroblast growth factor 7 into livers of diabetic mice leads to short‐term hepatocyte proliferation and improves islet engraftment with superior long term glycemic control versus transplantation with islets alone. See the editorial on page 2927.
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影响因子：
8
作者：
Liu S;Zhang L;Cheng J;Lu Y;Liu J
通讯作者：
Liu J
影响因子：
2.6
作者：
Fiaschi-Taesch, Nathalie;Stewart, Andrew F.;Garcia-Ocana, Adolfo
通讯作者：
Garcia-Ocana, Adolfo
影响因子：
64.8
作者：
Hart, AW;Baeza, N;Edlund, H
通讯作者：
Edlund, H
新型固相位点特异性聚乙二醇化增强重组人角质形成细胞生长因子 1 的体外和体内生物稳定性
影响因子：
3.7
作者：
Huang Z;Zhu G;Sun C;Zhang J;Zhang Y;Zhang Y;Ye C;Wang X;Ilghari D;Li X
通讯作者：
Li X
影响因子：
8.8
作者：
Brooks, A. M.;Walker, N.;Shaw, J. A. M.
通讯作者：
Shaw, J. A. M.