Human Bone Marrow Stromal Cell Exosomes Ameliorate Periodontitis

Author:

Yue C.1,Cao J.12,Wong A.1,Kim J.H.1,Alam S.1,Luong G.1,Talegaonkar S.1,Schwartz Z.3,Boyan B.D.3,Giannobile W.V.4ORCID,Sahingur S.E.5,Lin Z.1

Affiliation:

1. Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA

2. Department of Periodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, People’s Republic of China

3. Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA

4. Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA

5. Department of Periodontics, School of Dental Medicine, University of Pennsylvania, PA, USA

Abstract

Human bone marrow stromal cell (hBMSC)–derived exosomes are promising therapeutics for inflammatory diseases due to their unique microRNA (miRNA) and protein cargos. Periodontal diseases often present with chronicity and corresponding exuberant inflammation, which leads to loss of tooth support. In this study, we explored whether hBMSC exosomes can affect periodontitis progression. hBMSC exosomes were isolated from cell culture medium through sequential ultracentrifugation. miRNAs and proteins that were enriched in hBMSC exosomes were characterized by RNA sequencing and protein array, respectively. hBMSC exosomes significantly suppressed periodontal keystone pathogen Porphyromonas gingivalis–triggered inflammatory response in macrophages in vitro. Transcriptomic analysis suggested that exosomes exerted their effects through regulating cell metabolism, differentiation, and inflammation resolution. In vivo, weekly exosome injection into the gingival tissues reduced the tissue destruction and immune cell infiltration in rat ligature-induced periodontitis model. Collectively, these findings suggest that hBMSC-derived exosomes can potentially be used as a host modulation agent in the management of periodontitis.

Funder

National Cancer Institute

National Institute of Dental and Craniofacial Research

Publisher

SAGE Publications

Subject

General Dentistry

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