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通过3D培养系统获得高产的骨髓间充质干细胞衍生外泌体以促进皮肤伤口修复。

High-yield BMSC-derived exosomes by the 3D culture system to enhance the skin wound repair.

作者信息

Wu Jie, Li Siqi, Wang Hao, Qi Yuanbo, Tao Sheng, Tang Peifu, Liu Daohong

机构信息

Medical School of Chinese PLA, Beijing 100853, China.

Department of Orthopedics, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Regen Biomater. 2025 Apr 10;12:rbaf022. doi: 10.1093/rb/rbaf022. eCollection 2025.

Abstract

Wound defects pose a substantial challenge in clinical practice, often resulting in prolonged healing times and an elevated risk of infection. Insufficient vascularization is a critical factor that adversely affects wound healing. Exosomes obtained from bone mesenchymal stem cells (BMSC-exos) have demonstrated significant promise in accelerating tissue repair by promoting angiogenesis. However, their limited yield and suboptimal biological functions impede widespread clinical application in enhancing wound healing. Prior research has indicated that 3D cultures can boost exosome secretion when compared to conventional 2D cultures. However, the currently prevalent 3D culture methods often necessitate expensive equipment or cumbersome procedures. This study investigates a cost-effective and user-friendly 3D culture system developed using gelatin methacrylate (GelMA). Our findings indicate that a 5% concentration of GelMA provides an optimal environment for the 3D culture of BMSCs. Furthermore, we observed that 3D culture significantly delays the senescence of BMSCs, thereby creating favorable conditions for the sustained production of exosomes. Additionally, 3D cultivation has the potential to boost exosome secretion and enhance their angiogenic capabilities. experiments further confirmed that BMSC-exos from a 3D environment exhibit enhanced capabilities to promote wound healing. These results suggest that GelMA-based 3D cultures offer a novel strategy for both industrial production and clinical application of exosomes.

摘要

伤口缺损在临床实践中构成了重大挑战,常常导致愈合时间延长和感染风险升高。血管化不足是对伤口愈合产生不利影响的关键因素。从骨髓间充质干细胞获得的外泌体(BMSC-exos)已显示出通过促进血管生成来加速组织修复的巨大潜力。然而,它们有限的产量和欠佳的生物学功能阻碍了其在促进伤口愈合方面的广泛临床应用。先前的研究表明,与传统的二维培养相比,三维培养可以提高外泌体的分泌。然而,目前普遍使用的三维培养方法通常需要昂贵的设备或繁琐的程序。本研究调查了一种使用甲基丙烯酸明胶(GelMA)开发的具有成本效益且用户友好的三维培养系统。我们的研究结果表明,5%浓度的GelMA为骨髓间充质干细胞的三维培养提供了最佳环境。此外,我们观察到三维培养显著延迟了骨髓间充质干细胞的衰老,从而为外泌体的持续产生创造了有利条件。此外,三维培养有可能促进外泌体的分泌并增强其血管生成能力。实验进一步证实,来自三维环境的BMSC-exos具有更强的促进伤口愈合的能力。这些结果表明,基于GelMA的三维培养为外泌体的工业生产和临床应用提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239b/12041419/f2c7ab4a1db1/rbaf022f9.jpg

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