Exosomes derived from differentiated human ADMSC with the Schwann cell phenotype modulate peripheral nerve-related cellular functions.
Exosomes derived from differentiated human ADMSC with the Schwann cell phenotype modulate peripheral nerve-related cellular functions.
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DOI：
10.1016/j.bioactmat.2021.11.022
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发表时间：
2022-08
影响因子：
18.9
通讯作者：
Duan B
中科院分区：
文献类型：
--
作者：
Liu B;Kong Y;Shi W;Kuss M;Liao K;Hu G;Xiao P;Sankarasubramanian J;Guda C;Wang X;Lei Y;Duan B
由于功能恢复不理想和公共卫生负担，周围神经再生仍然是一个重大的临床挑战。外泌体，特别是来自间充质干细胞（MSCs）的外泌体，是促进神经再生的潜在无细胞治疗和基因治疗载体。在这项研究中，我们报道了人脂肪源性间质干细胞（hADMSCs）向雪旺细胞表型（hADMSCs - scs）的分化，然后从hADMSCs中分离出分化和未分化的外泌体（即dExo和uExo）。我们通过使用不同的周围神经相关细胞，评估并比较了uExo和dExo在抗氧化、血管生成、抗炎和促进轴突生长方面的作用。我们的研究结果表明，与未分化的hadmsc相比，hADMSC-SCs分泌更多的神经营养因子和其他生长因子。从hADMSC-SCs中分离的dExo可保护大鼠sc免受氧化应激，并增强HUVEC的迁移和血管生成。与uExo相比，dExo在下调促炎基因表达和细胞因子分泌、促进人诱导多能干细胞分化的感觉神经元轴突生长方面也有更好的表现。此外，microRNA （miRNA）测序分析显示，外泌体和它们的亲本细胞在miRNA谱上有一些相似之处，外泌体表现出不同的miRNA特征。在dExo中比在uExo中鉴定出更多的mirna。一些上调的mirna，如miRNA-132-3p和miRNA-199b-5p，与神经保护、抗炎症和血管生成高度相关。dExo可以有效调节各种周围神经相关的细胞功能，有望用于无细胞生物治疗以增强神经再生。来自具有SC表型的hADMSC-SCs的外泌体促进周围神经相关的细胞功能，包括抗氧化，血管生成，抗炎症和感觉神经元轴突生长。从hADMSCs中分离出外泌体，这些外泌体有或没有向SC表型分化（即dExo与uExo）。与未分化的hadmsc相比，hadmsc - sc分泌更多的生长因子。dExo保护大鼠sc免受氧化应激，促进内皮细胞迁移和血管生成。dExo促进hiPSCs分化的感觉神经元轴突生长。miRNA测序分析揭示并比较了外泌体和细胞miRNA谱。
Peripheral nerve regeneration remains a significant clinical challenge due to the unsatisfactory functional recovery and public health burden. Exosomes, especially those derived from mesenchymal stem cells (MSCs), are promising as potential cell-free therapeutics and gene therapy vehicles for promoting neural regeneration. In this study, we reported the differentiation of human adipose derived MSCs (hADMSCs) towards the Schwann cell (SC) phenotype (hADMSC-SCs) and then isolated exosomes from hADMSCs with and without differentiation (i.e., dExo vs uExo). We assessed and compared the effects of uExo and dExo on antioxidative, angiogenic, anti-inflammatory, and axon growth promoting properties by using various peripheral nerve-related cells. Our results demonstrated that hADMSC-SCs secreted more neurotrophic factors and other growth factors, compared to hADMSCs without differentiation. The dExo isolated from hADMSC-SCs protected rat SCs from oxidative stress and enhanced HUVEC migration and angiogenesis. Compared to uExo, dExo also had improved performances in downregulating pro-inflammatory gene expressions and cytokine secretions and promoting axonal growth of sensory neurons differentiated from human induced pluripotent stem cells. Furthermore, microRNA (miRNA) sequencing analysis revealed that exosomes and their parent cells shared some similarities in their miRNA profiles and exosomes displayed a distinct miRNA signature. Many more miRNAs were identified in dExo than in uExo. Several upregulated miRNAs, like miRNA-132-3p and miRNA-199b-5p, were highly related to neuroprotection, anti-inflammation, and angiogenesis. The dExo can effectively modulate various peripheral nerve-related cellular functions and is promising for cell-free biological therapeutics to enhance neural regeneration. Exosomes derived from hADMSC-SCs with the SC phenotype promote peripheral nerve-related cellular functions, including anti-oxidation, angiogenesis, anti-inflammation, and sensory neuron axonal growth. Exosomes were isolated from hADMSCs with and without differentiation towards SC phenotype (i.e., dExo vs uExo). hADMSC-SCs secreted more growth factors compared to hADMSCs without differentiation. The dExo protected rat SCs from oxidative stress and enhanced endothelial cell migration and angiogenesis. dExo promoted axonal growth of sensory neurons differentiated from hiPSCs. miRNA sequencing analysis unveiled and compared the exosomal and cellular miRNA profiles.
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影响因子：
3.3
作者：
Ding, Dah-Ching;Shyu, Woei-Cherng;Lin, Shinn-Zong
通讯作者：
Lin, Shinn-Zong
影响因子：
16
作者：
Dagur, Raghubendra Singh;Liao, Ke;Buch, Shilpa
通讯作者：
Buch, Shilpa
大鼠脂肪衍生的间充质干细胞的外泌体对挤压损伤后神经突生长和坐骨神经再生的影响。
影响因子：
5.1
作者：
Bucan V;Vaslaitis D;Peck CT;Strauß S;Vogt PM;Radtke C
通讯作者：
Radtke C
影响因子：
5.4
作者：
Antimisiaris SG;Mourtas S;Marazioti A
通讯作者：
Marazioti A
影响因子：
4.8
作者：
Balakrishnan A;Belfiore L;Chu TH;Fleming T;Midha R;Biernaskie J;Schuurmans C
通讯作者：
Schuurmans C