Transformed extracellular vesicles with high angiogenic ability as therapeutics of distal ischemic tissues.
Transformed extracellular vesicles with high angiogenic ability as therapeutics of distal ischemic tissues.
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DOI：
10.3389/fcell.2022.869850
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
简介：内皮祖细胞（EPC）在新生血管形成中的治疗作用已被提出；然而，迄今为止，关于EPC来源的细胞外囊泡（EV）拯救缺血组织的能力的研究还很少。为了研究EV用于缺血性疾病无细胞治疗的功能来源，我们在皮瓣小鼠模型中比较了EPC-EV和沃顿胶源间充质干细胞（WJ-EV）的功能。 结果和结论：我们的结果表明，在静脉注射中，EPC-EV（而非 WJ-EV）被缺血组织摄取。然而，EPC-EV诱导新血管形成和缺血组织恢复的能力较差。此外，与EPC-EV相比，WJ-EV在局部注射到小鼠体内时表现出更高的拯救缺血性损伤的能力。为了诱导高功能EPC-EV的分泌，将EPC用低氧预处理的WJ-EV内化，从而产生转化的hwEPC。与EPC相比，hwEPC表现出诱导血管生成基因和miRNA的增殖和上调，并促进血管生成能力。有趣的是，hwEPC 产生了一种修饰的 EV（hwEPC-EV），它高度表达与血管生成相关的 miRNA，例如 miR-155、miR-183 和 miR-296。此外，hwEPC-EV显着诱导缺血组织的新生血管形成，促进内皮细胞的增殖、VEGF和miR-183的表达以及血管生成功能。值得注意的是，与EPC-EV相比，hwEPC-EV被缺血组织高度摄取，并且在静脉内给药中在诱导缺血性损伤恢复方面表现出更大的效果。因此，hwEPC-EV可以被认为是治疗远端缺血组织的无细胞疗法的功能候选者。
Introduction: The therapeutic effects of endothelial progenitor cells (EPC) in neovascularization have been suggested; however, to date, few studies have been conducted on the ability of EPC-derived extracellular vesicles (EV) to rescue the ischemic tissues. In order to examine the functional sources of EV for cell-free therapy of ischemic diseases, we compared the functions of EPC-EV and those of Wharton’s Jelly-derived mesenchymal stem cell (WJ-EV) in the flap mouse model. Results and conclusion: Our results demonstrated that in the intravenous injection, EPC-EV, but not WJ-EV, were uptaken by the ischemic tissues. However, EPC-EV showed poor abilities to induce neovascularization and the recovery of ischemic tissues. In addition, compared to EPC-EV, WJ-EV showed a higher ability to rescue the ischemic injury when being locally injected into the mice. In order to induce the secretion of high-functional EPC-EV, EPC were internalized with hypoxic pre-treated WJ-EV, which resulted in a transformed hwEPC. In comparison to EPC, hwEPC showed induced proliferation and upregulation of angiogenic genes and miRNAs and promoted angiogenic ability. Interestingly, hwEPC produced a modified EV (hwEPC-EV) that highly expressed miRNAs related to angiogenesis, such as miR-155, miR-183, and miR-296. Moreover, hwEPC-EV significantly induced the neovascularization of the ischemic tissues which were involved in promoting the proliferation, the expression of VEGF and miR-183, and the angiogenic functions of endothelial cells. Of note, hwEPC-EV were highly uptaken by the ischemic tissues and showed a greater effect with regard to inducing recovery from ischemic injury in the intravenous administration, compared to EPC-EV. Therefore, hwEPC-EV can be considered a functional candidate for cell-free therapy to treat the distal ischemic tissues.
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影响因子：
3.9
作者：
Carolina E;Kato T;Khanh VC;Moriguchi K;Yamashita T;Takeuchi K;Hamada H;Ohneda O
通讯作者：
Ohneda O
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DOI：
10.1016/j.biocel.2019.01.017
发表时间：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
2.1
作者：
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Park, Ilyong
影响因子：
2.1
作者：
Ichioka, S;Minh, TC;Harii, K
通讯作者：
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影响因子：
7.5
作者：
Kong L;Wang Y;Wang H;Pan Q;Zuo R;Bai S;Zhang X;Lee WY;Kang Q;Li G
通讯作者：
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