State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China.
Biomaterials. 2019 Mar;196:18-30. doi: 10.1016/j.biomaterials.2017.10.046. Epub 2017 Oct 30.
Restoration of extensive bone loss and defects remain as an unfulfilled challenge in modern medicine. Given the critical contributions to bone homeostasis and diseases, mesenchymal stem cells (MSCs) have shown great promise to jumpstart and facilitate bone healing, with immense regenerative potential in both pharmacology-based endogenous MSC rescue/mobilization in skeletal diseases and emerging application of MSC transplantation in bone tissue engineering and cytotherapy. However, efficacy of MSC-based bone regeneration was not always achieved; particularly, fulfillment of MSC-mediated bone healing in diseased microenvironments of host comorbidities remains as a major challenge. Indeed, impacts of diseased microenvironments on MSC function rely not only on the dynamic regulation of resident MSCs by surrounding niche to convoy pathological signals of bone, but also on the profound interplay between transplanted MSCs and recipient components that mediates and modulates therapeutic effects on skeletal conditions. Accordingly, novel solutions have recently been developed, including improving resistance of MSCs to diseased microenvironments, recreating beneficial microenvironments to guarantee MSC-based regeneration, and usage of subcellular vesicles of MSCs in cell-free therapies. In this review, we summarize state-of-the-art knowledge regarding applications and challenges of MSC-mediated bone healing, further offering principles and effective strategies to optimize MSC-based bone regeneration in aging and diseases.
在现代医学中，广泛的骨损失和缺损的修复仍然是一个未满足的挑战。鉴于间充质干细胞（MSCs）对骨稳态和疾病的关键贡献，它们显示出极大的潜力来启动和促进骨愈合，在基于药理学的骨骼疾病内源性 MSC 抢救/动员和 MSC 移植在骨组织工程和细胞治疗中的新兴应用方面具有巨大的再生潜力。然而，基于 MSC 的骨再生的疗效并不总是能够实现；特别是，在宿主合并症的疾病微环境中实现 MSC 介导的骨愈合仍然是一个主要挑战。事实上，疾病微环境对 MSC 功能的影响不仅取决于周围龛位对骨病理信号的常驻 MSC 的动态调节，还取决于移植 MSC 与受体成分之间的深刻相互作用，这些相互作用调节和调节对骨骼状况的治疗效果。因此，最近开发了新的解决方案，包括提高 MSC 对疾病微环境的抵抗力，重新创造有益的微环境以保证基于 MSC 的再生，以及在无细胞治疗中使用 MSC 的亚细胞囊泡。在这篇综述中，我们总结了 MSC 介导的骨愈合的应用和挑战的最新知识，进一步提出了优化衰老和疾病中基于 MSC 的骨再生的原则和有效策略。
