Targeting central nervous system extracellular vesicles enhanced triiodothyronine remyelination effect on experimental autoimmune encephalomyelitis.
Targeting central nervous system extracellular vesicles enhanced triiodothyronine remyelination effect on experimental autoimmune encephalomyelitis.
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靶向中枢神经系统细胞外囊泡增强三碘甲腺原氨酸对实验性自身免疫性脑脊髓炎的髓鞘再生作用
DOI：
10.1016/j.bioactmat.2021.07.017
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发表时间：
2022-03
影响因子：
18.9
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Xiao Y;Tian J;Wu WC;Gao YH;Guo YX;Song SJ;Gao R;Wang LB;Wu XY;Zhang Y;Li X
缺乏靶向和高效的中枢神经系统（CNS）病灶药物递送是脱髓鞘病治疗的主要问题。细胞外囊泡（EVs）由于其先进的特性，作为一种药物传递载体具有很大的前景。然而，由于其靶向能力不足和全身给药后的“稀释效应”，临床应用受到限制。神经干细胞（NSCs）由于其非凡的自我更新能力，为电动汽车提供了丰富的来源。在这里，我们开发了一种新的治疗系统，使用高表达配体PDGF-A （EVPs）修饰的NSCs的EVs，并实现局部递送。研究表明，evp可显著增强少突胶质细胞谱系的靶向能力。此外，evp用于包埋三碘甲状腺原氨酸（T3），这是一种甲状腺激素，对少突胶质细胞的发育至关重要，但在全身给药时具有严重的副作用。我们的研究结果表明，与单独给药EVPs或T3相比，全身注射EVPs + T3可显著缓解实验性自身免疫性脑脊髓炎小鼠的疾病发展，增强少突胶质细胞存活，抑制髓磷脂损伤，促进髓磷脂再生。综上所述，我们的研究结果表明，工程化evp具有显著的中枢神经系统病变靶向潜力，为中枢神经系统脱髓鞘疾病和神经炎症提供了一种有效的治疗策略。EVPs + T3治疗可改善疾病发展并促进髓鞘再生。nsc衍生的EV-PDGFA显著提高了对OLGs谱系和中枢神经系统脱髓鞘区域的靶向效率。EVPs-T3在病变中发挥治疗作用，抑制疾病发展，保护髓磷脂损失。EVPs-T3增加了病变中OLGs的数量，TEM数据证明EVPs-T3促进了体内髓鞘再生。
The lack of targeted and high-efficiency drug delivery to the central nervous system (CNS) nidus is the main problem in the treatment of demyelinating disease. Extracellular vesicles (EVs) possess great promise as a drug delivery vector given their advanced features. However, clinical applications are limited because of their inadequate targeting ability and the “dilution effects” after systemic administration. Neural stem cells (NSCs) supply a plentiful source of EVs on account of their extraordinary capacity for self-renewal. Here, we have developed a novel therapeutic system using EVs from modified NSCs with high expressed ligand PDGF-A (EVPs) and achieve local delivery. It has been demonstrated that EVPs greatly enhance the target capability on oligodendrocyte lineage. Moreover, EVPs are used for embedding triiodothyronine (T3), a thyroid hormone that is critical for oligodendrocyte development but has serious side effects when systemically administered. Our results demonstrated that systemic injection of EVPs + T3, versus EVPs or T3 administration individually, markedly alleviated disease development, enhanced oligodendrocyte survival, inhibited myelin damage, and promoted myelin regeneration in the lesions of experimental autoimmune encephalomyelitis mice. Taken together, our findings showed that engineered EVPs possess a remarkable CNS lesion targeting potential that offers a potent therapeutic strategy for CNS demyelinating diseases as well as neuroinflammation. Schematic representation of EVPs + T3 treatment ameliorated disease development and promoted myelin regeneration. NSC-derived EV-PDGFA dramatically increased targeting efficiency to the lineage of OLGs and the demyelinated area in the CNS. EVPs-T3 exert the therapeutic ability in the lesion suppressed the disease development and protected myelin loss. EVPs-T3 increased numbers of OLGs in the lesion and TEM data evidenced that EVPs-T3 promotes myelin regeneration in vivo.
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DOI：
10.1126/science.aad2791
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Delong T;Wiles TA;Baker RL;Bradley B;Barbour G;Reisdorph R;Armstrong M;Powell RL;Reisdorph N;Kumar N;Elso CM;DeNicola M;Bottino R;Powers AC;Harlan DM;Kent SC;Mannering SI;Haskins K
通讯作者：
Haskins K
影响因子：
--
作者：
Abbaszadeh, Hojjat-Allah;Tiraihi, Taki;Taheri, Taher
通讯作者：
Taheri, Taher
DOI：
10.1016/j.mcn.2012.03.007
发表时间：
2012-05
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Dugas JC;Ibrahim A;Barres BA
通讯作者：
Barres BA
影响因子：
5.3
作者：
Geraci F;Ragonese P;Barreca MM;Aliotta E;Mazzola MA;Realmuto S;Vazzoler G;Savettieri G;Sconzo G;Salemi G
通讯作者：
Salemi G
影响因子：
16.2
作者：
MORSHEAD, CM;REYNOLDS, BA;VANDERKOOY, D
通讯作者：
VANDERKOOY, D