Engineered osteoclasts as living treatment materials for heterotopic ossification therapy.
Wenjing JinXianfeng LinHaihua PanChenchen ZhaoPengcheng QiuRuibo ZhaoZihe HuYanyan ZhouHaiyan WuXiao ChenChun-Hui YuanZhijian XieRuikang TangPublished in: Nature communications (2021)
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.
Keyphrases
- cell therapy
- induced apoptosis
- cell cycle arrest
- pi k akt
- bone loss
- bone mineral density
- chronic kidney disease
- gene expression
- hiv infected
- signaling pathway
- stem cells
- escherichia coli
- oxidative stress
- endoplasmic reticulum stress
- mesenchymal stem cells
- soft tissue
- postmenopausal women
- machine learning
- deep learning
- drug delivery