i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal.
INEB-Instituto de Engenharia Biomédica, University of Porto, 4200-465 Porto, Portugal.
Int J Mol Sci. 2019 Jul 12;20(14):3430. doi: 10.3390/ijms20143430.
The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.
正常的骨骼再生过程是一个复杂而协调的事件系列，涉及不同的细胞类型和分子。然而，在临界大小/大骨缺损中，这一过程受到损害，非愈合或延迟愈合仍然是一个主要的临床问题。需要新的策略来辅助当前的治疗方法。间充质干细胞（MSCs）能够促进骨再生。通过调节特定基因的表达水平，可以改善其有益效果，目的是刺激 MSC 增殖、成骨分化或其免疫调节能力。在这种情况下，对 MSCs 的基因工程有望进一步增强其促再生特性并加速骨愈合。本文综述了最有前途的分子候选物（蛋白编码和非编码转录本），并讨论了用于工程和递送 MSCs 的不同方法，主要集中在体内动物研究上。考虑到 MSC 分泌组在骨修复中的潜力，也讨论了这个主题。此外，还讨论了使用 MSC 进行骨再生的临床研究的有希望的结果。最后，我们讨论了使用 MSCs 或基因工程 MSCs 的优点和局限性，以及它们作为骨骨折再生/修复促进剂的潜力。
