Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan.
Front Endocrinol (Lausanne). 2023 Mar 22;14:1151429. doi: 10.3389/fendo.2023.1151429. eCollection 2023.
Systemic transplantation of mesenchymal stem cells (MSCs), such as bone marrow MSCs (BMMSCs) and stem cells from human exfoliated deciduous teeth (SHED), is considered a prominent treatment for osteopenia. However, the mechanism of action of the transplanted MSCs has been poorly elucidated. In the recipient target tissue, including bone and bone marrow, only a few donor MSCs can be detected, suggesting that the direct contribution of donor MSCs may not be expected for osteopenia treatment. Meanwhile, secretomes, especially contents within extracellular vesicles (EVs) released from donor MSCs (MSC-EVs), play key roles in the treatment of several diseases. In this context, administrated donor MSC-EVs may affect bone-forming function of recipient cells. In this review, we discuss how MSC-EVs contribute to bone recovery recipient tissue in osteopenia. We also summarize a novel mechanism of action of systemic administration of SHED-derived EVs (SHED-EVs) in osteopenia. We found that reduced telomerase activity in recipient BMMSCs caused the deficiency of microenvironmental modulating function, including bone and bone marrow-like niche formation and immunomodulation in estrogen-deficient osteopenia model mice. Systemic administration of SHED-EVs could exert therapeutic effects on bone reduction recovering the telomerase activity, leading to the rejuvenation of the microenvironmental modulating function in recipient BMMSCs, as seen in systemic transplantation of SHED. RNase-preconditioned donor SHED-EVs diminished the therapeutic benefits of administrated SHED-EVs in the recipient osteopenia model mice. These facts suggest that MSC-EV therapy targets the recipient BMMSCs to rejuvenate the microenvironmental modulating function telomerase activity, recovering bone density. We then introduce future challenges to develop the reproducible MSC-EV therapy in osteopenia.
系统移植间充质干细胞（MSCs），如骨髓间充质干细胞（BMMSCs）和人脱落乳牙干细胞（SHED），被认为是治疗骨质疏松症的一种突出疗法。然而，移植的 MSCs 的作用机制尚未得到充分阐明。在包括骨骼和骨髓在内的受者靶组织中，只能检测到少数供体 MSCs，这表明供体 MSCs 的直接贡献可能无法预期用于骨质疏松症的治疗。同时，分泌组，特别是供体 MSC 释放的细胞外囊泡（EVs）中的内容物，在多种疾病的治疗中发挥着关键作用。在这种情况下，给予的供体 MSC-EVs 可能会影响受者细胞的成骨功能。在这篇综述中，我们讨论了 MSC-EVs 如何促进骨质疏松症受者组织的骨恢复。我们还总结了系统给予 SHED 衍生的 EVs（SHED-EVs）在骨质疏松症中的一种新作用机制。我们发现，受者 BMMSCs 中端粒酶活性的降低导致微环境调节功能的缺陷，包括雌激素缺乏性骨质疏松症模型小鼠中的骨和骨髓样龛形成和免疫调节。系统给予 SHED-EVs 可以对骨减少发挥治疗作用，恢复端粒酶活性，从而使受者 BMMSCs 的微环境调节功能恢复活力，就像系统给予 SHED 一样。RNase 预处理的供体 SHED-EVs 减弱了给予的 SHED-EVs 在受者骨质疏松症模型小鼠中的治疗效果。这些事实表明，MSC-EV 治疗的靶标是受者 BMMSCs，以恢复微环境调节功能，端粒酶活性，恢复骨密度。然后，我们介绍了在骨质疏松症中开发可重复 MSC-EV 治疗的未来挑战。
