Mesenchymal stem cells as a gene delivery vehicle for successful islet transplantation.
Mesenchymal stem cells as a gene delivery vehicle for successful islet transplantation.
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DOI：
10.1007/s11095-011-0434-5
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发表时间：
2011-09
影响因子：
3.7
通讯作者：
Mahato, Ram I.
中科院分区：
文献类型：
--
作者：
Wu, Hao;Lu, Wenli;Mahato, Ram I.
目的探讨人骨髓间充质干细胞(HBMSCs)作为基因载体同时表达人肝细胞生长因子(HGF)和白细胞介素1受体拮抗剂(IL-1ra)改善胰岛移植效果。显微镜下观察hBMSCs的形态及与胰岛的亲和力。用酶联免疫吸附试验检测靶基因和内源性基因的表达。采用钙调素-AM/碘化丙啶染色观察hBMSCs对胰岛的保护作用，体内观察同种异体胰岛移植情况。免疫荧光检测胰岛功能及血运重建情况。非供体特异性hBMSCs与人胰岛具有很强的结合亲和力，保护了细胞的活性和功能。在与胰岛共培养之前，将编码人HGF和人IL-1ra的腺病毒(Adv-hHGF-hIL-1ra)转导hBMSCs，进一步保护其免受细胞凋亡的影响，有助于维持三维结构和形态，并促进胰岛素的分泌。将携带Adv-hHGF-hIL-1ra基因的人胰岛移植到链脲佐菌素诱导的糖尿病非肥胖糖尿病/严重联合免疫缺陷(NOD-SCID)小鼠肾包膜下，通过将血糖水平降至≤200 mg/dL最多15周来逆转糖尿病，并减少达到正常血糖所需的胰岛数量。单独移植胰岛的小鼠在移植后4周血糖水平回升至≥500 mg/dL。结果人骨髓间充质干细胞是改善胰岛移植效果的有效基因载体。
To evaluate the efficacy of human bone marrow-derived mesenchymal stem cells (hBMSCs) as gene delivery vehicles to simultaneously express human hepatocyte growth factor (HGF) and interleukin 1 receptor antagonist (IL-1Ra) to improve the outcome of islet transplantation. Morphology and islet-binding affinity of hBMSCs were checked by microscope. The expression of target genes and endogenous genes was determined by ELISA. Protection of islets by hBMSCs was evaluated in vitro by Calcein-AM/Propidium Iodide staining and in vivo by allogeneic islet transplantation study. Function and revascularization of islets was evaluated by immune fluorescence study. Non-donor-specific hBMSCs showed strong binding affinity to human islets and protected viability and function. Transduction of hBMSCs with adenovirus encoding human HGF and human IL-1Ra (Adv-hHGF-hIL-1Ra) prior to co-culturing with islets further protected from apoptotic cell death, helped maintain 3D structures and morphology, and enhanced insulin secretion. Transplantation of human islets reconstituted with Adv-hHGF-hIL-1Ra transduced hBMSCs under the kidney capsule of streptozotocin-induced diabetic non-obese diabetic/severe combined immunodeficient (NOD-SCID) mice reversed diabetes by reducing blood glucose levels to ≤200 mg/dL for up to 15 weeks and reduced the number of islets required to achieving normoglycemia. Blood glucose levels of mice transplanted with islets alone reversed to ≥500 mg/dL 4 weeks post-transplantation. Results indentified hBMSCs as effective gene delivery vehicles to improve the outcome of islet transplantation.
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DOI：
10.1073/pnas.0608249103
发表时间：
2006-11-14
影响因子：
11.1
作者：
Lee, Ryang Hwa;Seo, Min Jeong;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
影响因子：
4.9
作者：
Cheng, Guofeng;Zhu, Lin;Mahato, Ram I.
通讯作者：
Mahato, Ram I.
影响因子：
4.2
作者：
Allay, JA;Dennis, JE;Gerson, SL
通讯作者：
Gerson, SL
影响因子：
6.2
作者：
Nakano, M;Yasunami, Y;Ikeda, S
通讯作者：
Ikeda, S