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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1491962

Engineered Myeloid Precursors Differentiate into Osteoclasts and Resorb Heterotopic Ossification in Mice

Provisionally accepted
Cameron Rementer Cameron Rementer 1*Apichai Yavirach Apichai Yavirach 2,3*Worakanya Buranaphatthana Worakanya Buranaphatthana 2,4Philip A. Walczak Philip A. Walczak 1,2*Mei Speer Mei Speer 1*Kat Pierce Kat Pierce 1Subramanian Dharmarajan Subramanian Dharmarajan 1Elizabeth Leber Elizabeth Leber 1Bruce Sangiorzan Bruce Sangiorzan 5*Steven Bain Steven Bain 5Marta Scatena Marta Scatena 1Alexander Blümke Alexander Blümke 1,6Cecilia M. Giachelli Cecilia M. Giachelli 1*
  • 1 Department of Bioengineering, School Medicine, University of Washington, Seattle, United States
  • 2 Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, Washington, United States
  • 3 Department of Prosthodontic, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Chiang Mai, Thailand
  • 4 Department of Oral Biology and Oral Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Chiang Mai, Thailand
  • 5 Department of Orthopaedics and Sports Medicine, School of Medicine, University of Washington, Seattle, Washington, United States
  • 6 Department of Orthopedics and Trauma Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

The final, formatted version of the article will be published soon.

    Heterotopic ossification (HO) occurs following orthopedic trauma, spinal cord injuries, brain trauma and limb amputations. Once symptomatic, HO causes pain, limited mobility and decreased quality of life. Current treatments are limited and have significant complications with high recurrence rates, underscoring the need for improved therapeutic interventions. Osteoclasts (OCs) are physiological bone resorptive cells that secrete enzymes and protons to degrade bone. 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. 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. In summary, these data confirm 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.

    Keywords: heterotopic ossification, Osteoclasts, Engineered Osteoclasts, Rank, Chemical inducer of dimerization, Resorption

    Received: 05 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Rementer, Yavirach, Buranaphatthana, Walczak, Speer, Pierce, Dharmarajan, Leber, Sangiorzan, Bain, Scatena, Blümke and Giachelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Cameron Rementer, Department of Bioengineering, School Medicine, University of Washington, Seattle, United States
    Apichai Yavirach, Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, 98195, Washington, United States
    Philip A. Walczak, Department of Bioengineering, School Medicine, University of Washington, Seattle, United States
    Mei Speer, Department of Bioengineering, School Medicine, University of Washington, Seattle, United States
    Bruce Sangiorzan, Department of Orthopaedics and Sports Medicine, School of Medicine, University of Washington, Seattle, 98195-4550, Washington, United States
    Cecilia M. Giachelli, Department of Bioengineering, School Medicine, University of Washington, Seattle, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.