Engineered osteoclasts as living treatment materials for heterotopic ossification therapy

• Published in: Nature communications 2021-11, Vol.12 (1), p.6327-6327, Article 6327
• Main Authors: Jin, Wenjing, Lin, Xianfeng, Pan, Haihua, Zhao, Chenchen, Qiu, Pengcheng, Zhao, Ruibo, Hu, Zihe, Zhou, Yanyan, Wu, Haiyan, Chen, Xiao, Ouyang, Hongwei, Xie, Zhijian, Tang, Ruikang
• Format: Article
• Language: English
• Subjects: 13/21; 13/31; 14/19; 14/28; 14/3; 14/34; 14/63; 14/69; 147/135; 59; 631/1647/767/1424; 631/443/63; 631/45/2783; 631/61/51/1844; 64/60; 64/86; Animals; Biomedical materials; Bone and Bones; Bone demineralization; Bone growth; Bone Remodeling; Bone resorption; Calcification; Calcification (ectopic); Calcium; Cell Engineering; Cell Movement; Cell therapy; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humanities and Social Sciences; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Minerals; multidisciplinary; Ossification (ectopic); Ossification, Heterotopic - pathology; Ossification, Heterotopic - therapy; Osteoclasts; Osteoclasts - pathology; Osteogenesis; Plaques; Rats; Science; Science (multidisciplinary); Soft tissues; Tissue engineering
• ISSN: 2041-1723; 2041-1723
• 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. Heterotopic ossification (HO) is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these calcified plaques. Here, the authors demonstrate that chemically engineered osteoclasts coated with tetracycline can improve their targeting capacity to ectopic calcifications, which extends their bone resorption functions for the treatment of HO.