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包含bpV(pic)/PLGA微球的脱细胞脊髓支架促进脊髓损伤后的轴突再生和功能恢复。

Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury.

作者信息

Liu Jia, Li Kai, Huang Ke, Yang Chengliang, Huang Zhipeng, Zhao Xingchang, Song Shiqiang, Pang Taisen, Zhou Jing, Wang Yuhai, Wang Chong, Tang Yujin

机构信息

Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities 18 Zhongshan II Road Baise Guangxi 533000 China

Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital of Southern Medical University Guangzhou Guangdong 510000 China.

出版信息

RSC Adv. 2020 May 18;10(32):18677-18686. doi: 10.1039/d0ra02661a. eCollection 2020 May 14.

DOI:10.1039/d0ra02661a
PMID:35518337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9053942/
Abstract

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery. Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase AKT/mTOR activity and induce robust axonal elongation and regeneration. However, the therapeutic effect of bpV(pic) in treating SCI is limited due to the lack of efficient delivery approaches. In this study, a composite scaffold consisting of an acellular spinal cord (ASC) scaffold and incorporated bpV(pic) loaded poly (lactic--glycolic acid) (PLGA) microspheres was developed, in order to improve the therapeutic effect of bpV(pic) on SCI. The inhibition of PTEN activity and activation of the mTORC1/AKT pathway, the axonal regeneration and the markers of apoptosis were analyzed western blot and immunofluorescence . The bpV(pic)/PLGA/ASC scaffolds showed excellent biocompatibility and promoted the viability of neural stem cells and axonal growth . Implantation of the composite scaffold into rats with hemi-sectioned SCI resulted in increased axonal regeneration and functional recovery . Besides, bpV(pic) inhibited the phosphorylation of PTEN and activated the PI3K/mTOR signaling pathway. The successful construction of the composite scaffold improves the therapeutic effect of bpV(pic) on SCI.

摘要

脊髓损伤（SCI）是一种对中枢神经系统（CNS）的创伤性损伤，致残率高且自我恢复能力低。据报道，用双过氧钒（吡啶）（bpV（pic））进行药理学阻断抑制磷酸酶和张力蛋白同源物（PTEN）可增加AKT/mTOR活性，并诱导强大的轴突伸长和再生。然而，由于缺乏有效的递送方法，bpV（pic）治疗SCI的效果有限。在本研究中，开发了一种由脱细胞脊髓（ASC）支架和掺入负载bpV（pic）的聚（乳酸-乙醇酸）（PLGA）微球组成的复合支架，以提高bpV（pic）对SCI的治疗效果。通过蛋白质免疫印迹和免疫荧光分析PTEN活性的抑制、mTORC1/AKT途径的激活、轴突再生和细胞凋亡标志物。bpV（pic）/PLGA/ASC支架表现出优异的生物相容性，促进了神经干细胞的活力和轴突生长。将复合支架植入半横断SCI大鼠体内可增加轴突再生和功能恢复。此外，bpV（pic）抑制PTEN的磷酸化并激活PI3K/mTOR信号通路。复合支架的成功构建提高了bpV（pic）对SCI的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/78e02d1457af/d0ra02661a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/7ac13d941c7c/d0ra02661a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/10078828349c/d0ra02661a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/6a0f83502f87/d0ra02661a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/6acf17905bae/d0ra02661a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/78e02d1457af/d0ra02661a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/7ac13d941c7c/d0ra02661a-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/10078828349c/d0ra02661a-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/6a0f83502f87/d0ra02661a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/6acf17905bae/d0ra02661a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b575/9053942/78e02d1457af/d0ra02661a-f5.jpg

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