工程化破骨细胞作为异位骨化治疗的活治疗材料。
Engineered osteoclasts as living treatment materials for heterotopic ossification therapy.
机构信息
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, China.
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, 310006, China.
出版信息
Nat Commun. 2021 Nov 3;12(1):6327. doi: 10.1038/s41467-021-26593-1.
Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as "living treatment agents" for cell therapy.
破骨细胞（OCs）是唯一能够重塑骨骼的细胞，能够通过生物学方式脱矿化钙矿物质。由于活性、迁移和对异位钙化部位的黏附能力有限，幼稚的 OCs 在去除异位钙化方面存在局限性，例如异位骨化（HO）。HO 是指在骨骼外的软组织中形成病理性成熟骨，目前尚无可靠的方法去除这些意外的钙化斑块。在本研究中，我们开发了一种用四环素（TC）修饰 OCs 的化学方法，产生了具有增强靶向和黏附异位钙化组织能力的工程化 OCs（TC-OCs），这是由于对钙矿物质的广泛亲和力。与幼稚的 OCs 不同，TC-OCs 能够有效地在体外和体内去除 HO。这一成就表明，使用修饰的 OCs 可以逆转 HO，并为将细胞工程化为“活治疗剂”用于细胞治疗提供了希望。
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