Mesenchymal stem/stromal cells genetically engineered to produce vascular endothelial growth factor for revascularization in wound healing and ischemic conditions.
Mesenchymal stem/stromal cells genetically engineered to produce vascular endothelial growth factor for revascularization in wound healing and ischemic conditions.
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DOI：
10.1111/trf.14914
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发表时间：
2019-03
期刊：
影响因子：
2.9
通讯作者：
Nolta JA
中科院分区：
文献类型：
--
作者：
Fierro FA;Magner N;Beegle J;Dahlenburg H;Logan White J;Zhou P;Pepper K;Fury B;Coleal-Bergum DP;Bauer G;Gruenloh W;Annett G;Pifer C;Nolta JA
间充质干细胞(MSCs)可以主动寻找低氧区域并分泌促血管生成因子，因此可能能够改善缺血条件。然而，在更严重的创伤和慢性病例中，仅有细胞可能是不够的。因此，我们结合了干细胞和血管生成因子的方法来进行更有效的治疗。我们开发了一种设计用于治疗严重肢体缺血(CLI)的工程化干细胞治疗产品，该产品也可用于创伤导致的瘢痕形成和纤维化，在主血管受损和堵塞后需要额外的侧支血流。我们使用了来自正常人类捐赠者骨髓的MSCs，并对其进行了改造，使其产生高水平的血管生成因子血管内皮生长因子(VEGF)。MSC/VEGF产品已经成功地开发出来，并使用符合GMP的方法进行了表征，我们完成的实验表明，与每项研究中的生理盐水对照组相比，MSC/VEGF显著增加了免疫缺陷小鼠缺血肢体的血流量。我们还进行了安全性研究，证明注射的产品不会造成伤害，细胞在低氧预适应后在注射部位停留一个多月。一种按需配方系统正在开发中，用于将产品运送到缺乏细胞处理设施的临床地点。
Mesenchymal Stem/stromal Cells (MSCs) may be able to improve ischemic conditions as they can actively seek out areas of low oxygen and secrete pro-angiogenic factors. In more severe trauma and chronic cases, however, cells alone may not be enough. Therefore, we have combined the stem cell and angiogenic factor approaches to make a more potent therapy. We developed an engineered stem cell therapy product designed to treat critical limb ischemia (CLI), that could also be used in trauma-induced scarring and fibrosis where additional collateral bloodflow is needed following damage to and blockage of the primary vessels. We used MSCs from normal human donor bone marrow, and engineered them to produce high levels of the angiogenic factor Vascular Endothelial Growth Factor (VEGF). The MSC/VEGF product has been successfully developed and characterized using Good Manufacturing Practice (GMP) - compliant methods, and we have completed experiments showing that MSC/VEGF significantly increased blood flow in the ischemic limb of immune deficient mice, as compared to the saline controls in each study. We also performed safety studies, demonstrating that the injected product does not cause harm and that the cells remain around the injection site for over a month after hypoxic pre-conditioning. An on-demand formulation system for delivery of the product to clinical sites that lack cell processing facilities is in development.
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影响因子：
5.9
作者：
Chinnadurai, Raghavan;Garcia, Marco A.;Sakurai, Yumiko;Lam, Wilbur A.;Kirk, Allan D.;Galipeau, Jacques;Copland, Ian B.
通讯作者：
Copland, Ian B.
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
DOI：
10.1007/s40256-016-0210-3
发表时间：
2017-06
期刊：
American journal of cardiovascular drugs : drugs, devices, and other interventions
影响因子：
--
作者：
Deev R;Plaksa I;Bozo I;Isaev A
通讯作者：
Isaev A
影响因子：
37.8
作者：
Rajagopalan, S;Mohler, ER;Annex, BH
通讯作者：
Annex, BH
影响因子：
37.8
作者：
Losordo, DW;Vale, PR;Kuntz, RE
通讯作者：
Kuntz, RE