title: Conditioned Medium from Periodontal Ligament Stem Cells Enhances Periodontal Regeneration.
abstract: Periodontal disease is one of the most common infectious diseases in adults and is characterized by the destruction of tooth-supporting tissues. Mesenchymal stem cells (MSCs) comprise the mesoderm-originating stem cell population, which has been studied and used for cell therapy. However, because of the lower rate of cell survival after MSC transplantation in various disease models, paracrine functions of MSCs have been receiving increased attention as a regenerative mechanism. The aim of this study was to investigate the regenerative potential of transplanted conditioned medium (CM) obtained from cultured periodontal ligament stem cells (PDLSCs), the adult stem cell population in tooth-supporting tissues, using a rat periodontal defect model. Cell-free CM was collected from PDLSCs and fibroblasts, using ultrafiltration and transplanted into surgically created periodontal defects. Protein content of CM was examined by antibody arrays. Formation of new periodontal tissues was analyzed using microcomputed tomography and histological sections. PDLSC-CM transplantation enhanced periodontal tissue regeneration in a concentration-dependent manner, whereas fibroblast-CM did not show any regenerative function. Proteomic analysis revealed that extracellular matrix proteins, enzymes, angiogenic factors, growth factors and cytokines were contained in PDLSC-CM. Furthermore, PDLSC-CM transplantation resulted in the decreased mRNA level of tumor necrosis factor-α (TNF-α) in healing periodontal tissues. In addition, we found that PDLSC-CM suppressed the mRNA level of TNF-α in the monocyte/macrophage cell line, RAW cells, stimulated with IFN-γ. Our findings suggested that PDLSC-CM enhanced periodontal regeneration by suppressing the inflammatory response through TNF-α production, and transplantation of PDLSC-CM could be a novel approach for periodontal regenerative therapy.
authors.affiliation: 1 Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nagata
authors.affiliation: 2 Department of Nanomedicine (DNP), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Kengo
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: 1 Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Keiko
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: 2 Department of Nanomedicine (DNP), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Motohiro
authors.initials: M
authors.lastname: Komaki
authors.affiliation: 3 Department of Life Science, Research and Development Division for Applied Technology, Research and Development Center, Dai Nippon Printing Co., Ltd. , Chiba, Japan .
authors.forename: Naoki
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: 1 Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: 4 Department of Cellular Physiological Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo, Japan .
authors.forename: Ikuo
authors.initials: I
authors.lastname: Morita
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D010519:Periodontium / Q000293:injuries / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned
keywords: dental and periodontal; mesenchymal stem cells; wound healing