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Engineered osteoclasts as living treatment materials for heterotopic ossification therapy

Author

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  • Wenjing Jin

    (Zhejiang University
    Cancer Center of Zhejiang University)

  • Xianfeng Lin

    (Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Haihua Pan

    (Zhejiang University)

  • Chenchen Zhao

    (Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Pengcheng Qiu

    (Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Ruibo Zhao

    (Zhejiang Sci-Tech University)

  • Zihe Hu

    (Cancer Center of Zhejiang University)

  • Yanyan Zhou

    (Cancer Center of Zhejiang University)

  • Haiyan Wu

    (Cancer Center of Zhejiang University)

  • Xiao Chen

    (Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Hongwei Ouyang

    (Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Zhijian Xie

    (Cancer Center of Zhejiang University)

  • Ruikang Tang

    (Zhejiang University
    Zhejiang University)

Abstract

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.

Suggested Citation

  • Wenjing Jin & Xianfeng Lin & Haihua Pan & Chenchen Zhao & Pengcheng Qiu & Ruibo Zhao & Zihe Hu & Yanyan Zhou & Haiyan Wu & Xiao Chen & Hongwei Ouyang & Zhijian Xie & Ruikang Tang, 2021. "Engineered osteoclasts as living treatment materials for heterotopic ossification therapy," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26593-1
    DOI: 10.1038/s41467-021-26593-1
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    References listed on IDEAS

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    1. Zhenping Cao & Xinyue Wang & Yan Pang & Shanshan Cheng & Jinyao Liu, 2019. "Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. William J. Boyle & W. Scott Simonet & David L. Lacey, 2003. "Osteoclast differentiation and activation," Nature, Nature, vol. 423(6937), pages 337-342, May.
    3. Peng Shi & Nan Zhao & James Coyne & Yong Wang, 2019. "DNA-templated synthesis of biomimetic cell wall for nanoencapsulation and protection of mammalian cells," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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