Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke.
Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke.
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在缺血性卒中大鼠模型中，来自脑提取的间充质干细胞的微泡改善了神经功能。
DOI：
10.1038/srep33038
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发表时间：
2016-09-09
影响因子：
4.6
通讯作者：
Kim HS
中科院分区：
文献类型：
--
作者：
Lee JY;Kim E;Choi SM;Kim DW;Kim KP;Lee I;Kim HS
据报道，间充质干细胞（MSC）的移植可以改善缺血性卒中大鼠模型的功能结局，随后的研究表明，MSC衍生的微泡（MV）可以取代MSC的有益作用。在这里，我们评估了三种不同的MSC衍生的MV，包括来自未处理的MSC的MV（MSC-MV），来自用正常大鼠脑提取物处理的MSC的MV（NBE-MSC-MV），以及来自用中风损伤的大鼠脑提取物处理的MSC的MV（SBE-MSC-MV），并测试它们对大鼠永久性大脑中动脉闭塞（pMCAO）诱导的缺血性脑损伤的影响。NBE-MSC-MV和SBE-MSC-MV在改善缺血性脑损伤和改善功能恢复方面的疗效显著高于MSC-MV。我们在NBE-MSC-MV和SBE-MSC-MV中发现了相似的关键信号蛋白谱，这解释了它们相似的治疗功效。免疫组织化学分析表明，脑提取物处理的MSC-MV减少炎症，增强血管生成，并增加大鼠大脑中的内源性神经发生。我们进行了质谱蛋白质组学分析，发现脑提取物处理的MSC-MV的总蛋白质组高度富集已知的囊泡蛋白。值得注意的是，脑提取物上调的MSC-MV蛋白往往是组织修复途径的模块。我们认为，由脑微环境刺激的MSC-MV蛋白是增强MSC治疗中风损伤的旁分泌效应物。
Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury.
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影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
3.3
作者：
Boltze, Johannes;Schmidt, Uwe R.;Schaebitz, Wolf-Ruediger
通讯作者：
Schaebitz, Wolf-Ruediger
影响因子：
2.9
作者：
BORLONGAN, CV;CAHILL, DW;SANBERG, PR
通讯作者：
SANBERG, PR
人骨髓间充质干细胞来源的细胞外囊泡促进大鼠心肌梗死模型中的血管生成
影响因子：
4.7
作者：
Bian, Suyan;Zhang, Liping;Yu, Hepeng
通讯作者：
Yu, Hepeng