An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration.
An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration.
复制标题
预修饰胚胎髓核祖细胞的酯酶敏感型布洛芬纳米胶束促进椎间盘退变的再生。
DOI：
10.1016/j.bioactmat.2022.07.024
复制
发表时间：
2023-03
影响因子：
18.9
通讯作者：
Liang, Cheng-zhen
中科院分区：
文献类型：
--
作者：
Xia, Kai-shun;Li, Dong-don;Wang, Cheng-gui;Ying, Li-wei;Wang, Jing-kai;Yang, Biao;Shu, Jia-wei;Huang, Xian-peng;Zhang, Yu-ang;Yu, Chao;Zhou, Xiao-peng;Li, Fang-cai;Slater, Nigel K. H.;Tang, Jian-bin;Chen, Qi-xin;Liang, Cheng-zhen
关键词：
基于干细胞的移植是治疗椎间盘退变（IDD）的一种有前景的方法。目前干细胞的局限性包括细胞来源不足、增殖能力差、髓核(NP)特异性分化潜力低以及移植后无法避免酸性IDD微环境引起的细胞焦亡。为了应对这些挑战，制备了胚胎来源的长期可扩张髓核祖细胞（NPPC）和酯酶响应性布洛芬纳米胶束（PEG-PIB）用于协同移植。在本研究中，我们提出了生物材料预修饰细胞策略； PEG-PIB被内吞，通过抑制焦亡来预修饰NPPC，使其适应恶劣的IDD微环境。结果表明，PEG-PIB预修饰的NPPCs在体外具有抑制细胞焦亡的作用；它们的进一步协同移植产生了有效的功能恢复、组织学再生以及 IDD 再生过程中细胞焦亡的抑制。在此，我们提供了一种新型生物材料预修饰细胞协同移植策略，在 IDD 再生中具有良好的治疗效果。建立并表征了长期可扩增的小鼠和人类胚胎衍生的 NPPC 系。制备 PEG-PIB 来预修饰 NPPC 以进行协同移植。 PEG-PIB 预修饰的 NPPC 可以抑制退变椎间盘内的细胞焦亡。
Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration. Long-term expandable mouse and human embryo derived NPPC lines are established and characterized. PEG-PIB are prepared to pre-modify NPPCs for synergistic transplantation. PEG-PIB pre-modified NPPCs can inhibit pyroptosis within degenerated intervertebral disc.
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影响因子：
4.9
作者：
Erwin WM;Islam D;Inman RD;Fehlings MG;Tsui FW
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
Xue L;Yi H;Huang Z;Shi YB;Li WX
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Li WX
影响因子：
3
作者：
Gruber, Helen E.;Ingram, Jane A.;Hanley, Edward N., Jr.
通讯作者：
Hanley, Edward N., Jr.
影响因子：
7.5
作者：
Dicks, Amanda;Wu, Chia-Lung;Guilak, Farshid
通讯作者：
Guilak, Farshid