A Paradigm Shift in Bone Regeneration Therapy: Using Mesenchymal Stem Cells and the CRISPR-Cas9 Technology
A Paradigm Shift in Bone Regeneration Therapy: Using Mesenchymal Stem Cells and the CRISPR-Cas9 Technology
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发表时间：
2021
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通讯作者：
T. Narai;Yuji Nakayama;Isamu Kodani;K. Kokura
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作者：
T. Narai;Yuji Nakayama;Isamu Kodani;K. Kokura
目前骨再生治疗的主流方法是自体骨移植和人工骨/骨替代材料。然而，尚未取得令人满意的治疗效果。毫无疑问，间充质干细胞（MSC）是用于骨再生治疗的有用“工具”，并且已经期望MSC的使用。然而，由于其有限的成骨分化能力和在移植部位的效率，MSC细胞仍然没有广泛用于骨再生治疗。因此，从分子和细胞水平上对成骨分化进行解剖和调控是解决这一问题的关键。为此，细胞工程是一种很有前途的方法之一，各种有价值的工具，细胞工程已开发在最近几年。特别是，规则间隔的短回文重复序列-CRISPR相关蛋白9（CRISPR-Cas9）已经彻底改变了基因组编辑技术。通过利用基因修饰的MSC或由这种修饰的MSC衍生的成骨细胞，成骨分化过程应该更容易理解和可控。换句话说，这些技术可能具有标准化和优化骨再生治疗结果的潜力，迄今为止观察到广泛的个体差异。因此，在骨再生治疗期间可以实现减少的手术侵入、稳定的治疗结果和更短的治疗。在本文中，我们讨论了这种间充质干细胞的潜在治疗和临床应用，并通过基因组编辑工具，特别是CRISPR-Cas9技术，在骨再生治疗中的发展。
The current mainstream approach to bone regeneration treatment is autologous bone grafting and artificial bone/ bone substitute materials. However, satisfactory treatment results have not been achieved. There is no doubt that Mesenchymal Stem Cells (MSCs) are a useful "tool" for bone regeneration therapy and use of MSCs has been desired. However, MSCs cells are still not widely used in bone regeneration treatments due to their limited osteogenic differentiation ability and efficiency at the transplanted site. Thus, dissection and control of osteogenic differentiation in molecular and cellular level are keys to overcome this issue. To this end, cellular engineering is one of promising approach for it, and various valuable tools for cellular engineering have been developed in recent years. In particular, Clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) has revolutionized genome editing techniques. By utilizing genetically modified MSCs or osteogenic cells derived from such modified MSCs, osteogenic differentiation process should be more understandable and controllable. In other words, these technologies may have a potential to standardize and optimize bone regeneration treatment outcomes that so far wide individual differences are observed. Then, as a result, reduced surgical invasion, stable treatment results, and shorter treatment may be achieved during bone regeneration treatments. In this review, we discuss the potential therapeutic and clinical application of this mesenchymal stem cell and its development by means of genome editing tool, CRISPR-Cas9 technology in particular, in bone regeneration therapy.