Injectable exosome-functionalized extracellular matrix hydrogel for metabolism balance and pyroptosis regulation in intervertebral disc degeneration.
Injectable exosome-functionalized extracellular matrix hydrogel for metabolism balance and pyroptosis regulation in intervertebral disc degeneration.
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可注射外泌体功能化细胞外基质水凝胶用于椎间盘退变的代谢平衡和细胞凋亡调节。
DOI：
10.1186/s12951-021-00991-5
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发表时间：
2021-09-06
影响因子：
10.2
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Xing H;Zhang Z;Mao Q;Wang C;Zhou Y;Zhou X;Ying L;Xu H;Hu S;Zhang N
外泌体治疗是椎间盘退变（IVDD）的一种有前途的治疗方法，并且通过持续释放microRNA、蛋白质和转录因子来调节代谢紊乱、微环境和细胞稳态来实现其治疗效果。然而，外泌体的快速清除和破坏是外泌体治疗在IVDD中应用的两个主要挑战。本文中，制备了与脂肪来源的间充质干细胞（ADSC）外泌体（dECM@exo）偶联的热敏性脱细胞外基质（ECM）水凝胶以改善IVDD，所述外泌体继承了髓核组织和ADSC的上级性质。这种热敏性dECM@exo水凝胶系统不仅可以提供原位凝胶化以补充髓核细胞（NPC）中的ECM渗漏，而且还可以提供NPC生长的环境。此外，ADSC衍生的外泌体从该系统的持续释放通过调节基质金属蛋白酶（MMP）来调节基质合成和降解，并通过减轻体外炎症反应来抑制焦亡。动物结果表明，dECM@exo水凝胶系统维持了早期IVD微环境的稳态并改善了IVD。该功能系统可作为IVD药物递送和生物治疗的强大平台，以及IVDD的替代疗法。在线版本包含补充材料，可通过10.1186/s12951-021-00991-5获得。
Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) and achieves its therapeutic effects by regulating metabolic disorders, the microenvironment and cell homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for the application of exosome therapy in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes (dECM@exo) that inherits the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can provide not only in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD. The online version contains supplementary material available at 10.1186/s12951-021-00991-5.
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影响因子：
3
作者：
BUCKWALTER, JA
通讯作者：
BUCKWALTER, JA
影响因子：
7.3
作者：
Le Maitre, CL;Freemont, AJ;Hoyland, JA
通讯作者：
Hoyland, JA
影响因子：
10.9
作者：
Alzhavan, Omid;Ghaderi, Elham;Shahsavar, Mahla
通讯作者：
Shahsavar, Mahla
DOI：
10.1007/s10856-021-06495-w
发表时间：
2021-03-08
期刊：
Journal of materials science. Materials in medicine
影响因子：
--
作者：
Hejazi F;Ebrahimi V;Asgary M;Piryaei A;Fridoni MJ;Kermani AA;Zare F;Abdollahifar MA
通讯作者：
Abdollahifar MA
影响因子：
10.9
作者：
Kang, Seokyung;Park, Jong Bo;Kim, Byung-Soo
通讯作者：
Kim, Byung-Soo