Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.
Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.
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鼻内施用人类MSC用于小鼠缺血性脑损伤：体外和体内神经增合功能。
DOI：
10.1371/journal.pone.0112339
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Heijnen CJ
中科院分区：
文献类型：
--
作者：
Donega V;Nijboer CH;Braccioli L;Slaper-Cortenbach I;Kavelaars A;van Bel F;Heijnen CJ
在新生儿缺氧缺血（HI）小鼠模型中，C57 BL/6 MSC鼻内治疗可减少病变体积并改善运动和认知行为。在这项研究中，我们研究了人骨髓间充质干细胞（hMSCs）治疗新生小鼠HI脑损伤的潜力。评估hMSCs的再生能力对于将我们的知识转化为临床至关重要。我们确定了hMSCs在体外和体内的神经再生潜力，鼻内给药后10天HI新生小鼠。在P9小鼠幼仔中诱导HI。HI后10 d鼻内注射1×106或2×106 hMSCs。HI后28 d测量运动行为和病变体积。采用transwell共培养分化试验检测hMSCs体外诱导小鼠神经干细胞（mNSC）分化的能力。为了确定哪些趋化因子可能在介导MSC向病变迁移中发挥作用，我们在假手术后10天以及HI后10天和17天对84种趋化因子进行了PCR阵列。我们的研究结果表明，2×106 hMSCs减少病变体积，改善运动行为，减少瘢痕形成和小胶质细胞活性。此外，我们证明了分化试验反映了hMSCs在体内的神经再生潜力，因为hMSCs在体外诱导mNSCs分化为神经元。我们还提供了趋化因子CXCL 10可能在hMSC迁移到病变部位中发挥重要作用的证据。我们的发现表明，CXCL 10在HI后10天显著上调，但在HI后17天没有，当鼻内给予时，此时MSC不再到达病变。这项工作中描述的结果也诱使我们考虑hMSCs不仅作为新生儿脑病的潜在治疗选择，而且还用于神经系统的过多退行性和创伤性损伤。
Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI) mouse model. In this study, we investigated the potential of human MSCs (hMSCs) to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×106 or 2×106 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC) was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×106 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.
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影响因子：
3.7
作者：
Donega V;van Velthoven CT;Nijboer CH;van Bel F;Kas MJ;Kavelaars A;Heijnen CJ
通讯作者：
Heijnen CJ
影响因子：
5.3
作者：
Donega, Vanessa;Nijboer, Cora H.;Heijnen, Cobi J.
通讯作者：
Heijnen, Cobi J.
影响因子：
25
作者：
van Praag, H;Kempermann, G;Gage, FH
通讯作者：
Gage, FH
影响因子：
6.2
作者：
Tse, WT;Pendleton, JD;Guinan, EC
通讯作者：
Guinan, EC
影响因子：
3.6
作者：
Borlongan CV;Weiss MD
通讯作者：
Weiss MD