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热稳定性碱性成纤维细胞生长因子增强人牙髓间充质干细胞来源细胞外囊泡的产生和活性。

Thermostable Basic Fibroblast Growth Factor Enhances the Production and Activity of Human Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles.

机构信息

Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.

R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Nov 17;24(22):16460. doi: 10.3390/ijms242216460.

Abstract

Wharton's jelly-derived mesenchymal stem cell (WJ-MSC)-derived exosomes contain a diverse cargo and exhibit remarkable biological activity, rendering them suitable for regenerative and immune-modulating functions. However, the quantity of secretion is insufficient. A large body of prior work has investigated the use of various growth factors to enhance MSC-derived exosome production. In this study, we evaluated the utilization of thermostable basic fibroblast growth factor (TS-bFGF) with MSC culture and exosome production. MSCs cultured with TS-bFGF displayed superior proliferation, as evidenced by cell cycle analysis, compared with wild-type bFGF (WT-bFGF). Stemness was assessed through mRNA expression level and colony-forming unit (CFU) assays. Furthermore, nanoparticle tracking analysis (NTA) measurements revealed that MSCs cultured with TS-bFGF produced a greater quantity of exosomes, particularly under three-dimensional culture conditions. These produced exosomes demonstrated substantial anti-inflammatory and wound-healing effects, as confirmed by nitric oxide (NO) assays and scratch assays. Taken together, we demonstrate that utilization of TS-bFGF for WJ-MSC-derived exosome production not only increases exosome yield but also enhances the potential for various applications in inflammation regulation and wound healing.

摘要

Wharton 胶源间充质干细胞(WJ-MSC)衍生的外泌体含有多样化的货物,并表现出显著的生物学活性,使其适合于再生和免疫调节功能。然而,分泌量不足。大量先前的研究已经探讨了使用各种生长因子来增强 MSC 衍生的外泌体产生。在这项研究中,我们评估了热稳定碱性成纤维细胞生长因子(TS-bFGF)在 MSC 培养和外泌体产生中的应用。通过细胞周期分析,与野生型碱性成纤维细胞生长因子(WT-bFGF)相比,用 TS-bFGF 培养的 MSC 显示出更好的增殖能力。通过 mRNA 表达水平和集落形成单位(CFU)测定评估干性。此外,纳米颗粒跟踪分析(NTA)测量表明,在三维培养条件下,用 TS-bFGF 培养的 MSC 产生了更多的外泌体。通过一氧化氮(NO)测定和划痕测定证实,这些产生的外泌体具有显著的抗炎和伤口愈合作用。总之,我们证明了使用 TS-bFGF 进行 WJ-MSC 衍生的外泌体生产不仅可以增加外泌体的产量,还可以增强其在炎症调节和伤口愈合等各种应用中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e5f/10671285/15b5f60b4452/ijms-24-16460-g001.jpg

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