Engineered osteoclasts as living treatment materials for heterotopic ossification therapy

Wenjing Jin, Xianfeng Lin, Haihua Pan, Chenchen Zhao, Pengcheng Qiu, Ruibo Zhao, Zihe Hu, Yanyan Zhou, Haiyan Wu, Xiao Chen, Hongwei Ouyang, Zhijian Xie () and Ruikang Tang ()
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Wenjing Jin: Zhejiang University
Xianfeng Lin: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University
Haihua Pan: Zhejiang University
Chenchen Zhao: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University
Pengcheng Qiu: Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University
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
Hongwei Ouyang: Zhejiang University School of Medicine
Zhijian Xie: Cancer Center of Zhejiang University
Ruikang Tang: Zhejiang University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26593-1

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