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人尿源干细胞衍生的外泌体可改善白细胞介素-1β诱导的椎间盘退变。

Exosomes derived from human urine-derived stem cells ameliorate IL-1β-induced intervertebral disk degeneration.

机构信息

Department of Orthopedics, Shanghai Fifth People's Hospital, Fudan University, No. 801, Heqing Road, Minhang District, Shanghai, 200240, China.

出版信息

BMC Musculoskelet Disord. 2024 Jul 12;25(1):537. doi: 10.1186/s12891-024-07636-2.

DOI:10.1186/s12891-024-07636-2
PMID:38997667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11241922/
Abstract

BACKGROUND

Human intervertebral disk degeneration (IVDD) is a sophisticated degenerative pathological process. A key cause of IVDD progression is nucleus pulposus cell (NPC) degeneration, which contributes to excessive endoplasmic reticulum stress in the intervertebral disk. However, the mechanisms underlying IVDD and NPC degeneration remain unclear.

METHODS

We used interleukin (IL)-1β stimulation to establish an NPC-degenerated IVDD model and investigated whether human urine-derived stem cell (USC) exosomes could prevent IL-1β-induced NPC degeneration using western blotting, quantitative real-time polymerase chain reaction, flow cytometry, and transcriptome sequencing techniques.

RESULTS

We successfully extracted and identified USCs and exosomes from human urine. IL-1β substantially downregulated NPC viability and induced NPC degeneration while modulating the expression of SOX-9, collagen II, and aggrecan. Exosomes from USCs could rescue IL-1β-induced NPC degeneration and restore the expression levels of SOX-9, collagen II, and aggrecan.

CONCLUSIONS

USC-derived exosomes can prevent NPCs from degeneration following IL-1β stimulation. This finding can aid the development of a potential treatment strategy for IVDD.

摘要

背景

人类椎间盘退变(IVDD)是一个复杂的退行性病理过程。椎间盘退变的一个关键原因是髓核细胞(NPC)退变,这导致椎间盘内质网应激过度。然而,IVDD 和 NPC 退变的机制仍不清楚。

方法

我们使用白细胞介素(IL)-1β刺激建立 NPC 退变的 IVDD 模型,并使用 Western blot、实时定量聚合酶链反应、流式细胞术和转录组测序技术研究人尿源性干细胞(USC)外泌体是否可以预防 IL-1β诱导的 NPC 退变。

结果

我们成功地从人尿中提取并鉴定了 USCs 和外泌体。IL-1β 显著降低 NPC 的活力并诱导 NPC 退变,同时调节 SOX-9、胶原 II 和聚集蛋白聚糖的表达。USC 衍生的外泌体可挽救 IL-1β 诱导的 NPC 退变并恢复 SOX-9、胶原 II 和聚集蛋白聚糖的表达水平。

结论

USC 衍生的外泌体可预防 NPC 在 IL-1β 刺激后发生退变。这一发现可以为 IVDD 的潜在治疗策略的发展提供帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e3/11241922/e7d75aba6ca9/12891_2024_7636_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e3/11241922/c9479a7cc178/12891_2024_7636_Fig5_HTML.jpg
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The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes for Orthopedic Diseases Treatment.间充质干细胞及其衍生的外泌体在骨科疾病治疗中的潜在应用。
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