Engineered myeloid precursors differentiate into osteoclasts and resorb heterotopic ossification in mice

工程化髓系前体细胞在小鼠中分化为破骨细胞并吸收异位骨化

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作者:Cameron Rementer #, Apichai Yavirach #, Worakanya Buranaphatthana #, Philip A Walczak #, Mei Speer, Kat Pierce, Subramanian Dharmarajan, Elizabeth Leber, Bruce Sangiorzan, Steven Bain, Marta Scatena, Alexander Blümke #, Cecilia M Giachelli #

Discussion

In summary, these data con rm the ability of engineered myeloid precursors to differentiate into OCs and resorb HO in vivo paving the way for OC delivery as a promising approach for HO treatment.

Methods

In this study, we describe the use of genetically engineered OCs as a novel cell therapy approach to treat HO. Inducible, engineered myeloid precursors (iRANK cells) treated with a chemical inducer of dimerization (CID) differentiated into TRAP+ multinucleated OCs and resorbed mineralized tissues in vitro.

Results

In vivo, BMP-2-induced murine HO lesions were significantly regressed following treatment using iRANK cells with concomitant systemic administration of CID. Moreover, many OCs were TRAP+, MMP9+, and GFP+, indicating that they differentiated from delivered iRANK cells.

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