Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney , Sydney, Australia .
Tissue Eng Part A. 2017 Nov;23(21-22):1212-1220. doi: 10.1089/ten.tea.2016.0548. Epub 2017 Mar 23.
Mesenchymal stem cells (MSCs) have been widely used for tissue repair and regeneration. However, the inherent drawbacks, including limited cell survival after cell transplantation, have hindered direct MSC transplantation for tissue repair and regeneration. The aim of this study was to investigate if exosomes isolated from MSCs can promote the proliferation and differentiation of human primary osteoblastic cells (HOBs) and be potentially used for bone tissue regeneration. We showed that adipose tissue-derived MSC (ASC)-derived exosomes (ASC-EXO) were able to promote the proliferation and osteogenic differentiation in HOBs; and the trophic effects of ASC-EXO on HOBs were further harnessed when ASCs were preconditioned with tumor necrosis factor-alpha (TNF-α) for 3 days, which mimics the acute inflammatory phase upon bone injury. In addition, we showed that Wnt-3a content was elevated in ASC-EXO when ASCs were preconditioned by TNF-α, and inhibiting Wnt signaling decreased the osteogenic gene expression levels in HOBs which were cultured in TNF-α preconditioned ASCs conditioned medium. In conclusion, it was demonstrated that ASC-EXO, especially primed by TNF-α preconditioning on ASCs, offer a promising approach to replace direct stem cell transplantation for bone repair and regeneration.
间充质干细胞（MSCs）已被广泛用于组织修复和再生。然而，其内在的缺陷，包括细胞移植后细胞存活率有限，阻碍了直接 MSC 移植用于组织修复和再生。本研究旨在探讨是否可以从间充质干细胞中分离的外泌体促进人原代成骨细胞（HOBs）的增殖和分化，并可能用于骨组织再生。我们表明，脂肪组织来源的 MSC（ASC）衍生的外泌体（ASC-EXO）能够促进 HOBs 的增殖和成骨分化；并且当 ASC 用肿瘤坏死因子-α（TNF-α）预处理 3 天时，ASC-EXO 对 HOBs 的营养作用进一步被利用，这模拟了骨损伤时的急性炎症期。此外，我们表明，当 ASC 被 TNF-α预处理时，ASC-EXO 中的 Wnt-3a 含量升高，并且抑制 Wnt 信号降低了在 TNF-α预处理的 ASC 条件培养基中培养的 HOBs 的成骨基因表达水平。总之，证明 ASC-EXO，特别是通过 TNF-α 预处理 ASC 来启动，为替代直接干细胞移植用于骨修复和再生提供了一种有前途的方法。
