title: Circulating nucleated peripheral blood cells contribute to early-phase meniscal healing.
abstract: The purpose of this study was to assess how peripheral blood cells (PBCs) contribute to meniscus repair, using a parabiotic rat model. Wild-type (WT) and green fluorescent protein (GFP) transgenic rats were conjoined at the torso. After 4 weeks, the anterior part of the medial meniscus of both groups of rats was removed. At 1, 2, 4, 8 and 12 weeks post-meniscectomy, repaired tissue was evaluated using stereomicroscopy, histology with toluidine blue staining, and immunofluorescence microscopy. Stereomicroscopic observations and confocal laser microscopy revealed that a high number of GFP-positive cells were present in the repaired meniscus of WT rats 1 week post-meniscectomy, and the number of GFP-positive cells decreased over time. Based on blood chimerism, the ratios of PBCs in the repaired meniscus were 20.5 ± 2.3% at 1 week, 8.3 ± 0.9% at 2 weeks, 4.4 ± 0.9% at 4 weeks, 2.1 ± 0.9% at 8 weeks, and 0.5 ± 0.4% at 12 weeks, post-meniscectomy. Histologically, fibrochondrocytes were observed in the repaired meniscus of WT rats after 4 weeks, some of which were GFP-positive. The chondrogenic marker, type II collagen, was merged within the PBCs in the repaired tissue. However, type-II-collagen-positive cell ratio and metachromasia in the repaired meniscus were not equivalent in normal meniscal tissue. This indicated that PBCs were present within the repaired meniscus at an early phase, replacing the excised meniscal cells, suggesting PBCs contributed to meniscal healing. The tissue repair contribution by these cells decreased at later phases. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinya
authors.identifier: 0000-0002-3041-5616
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Junsei
authors.initials: J
authors.lastname: Takigami
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shozaburo
authors.initials: S
authors.lastname: Terai
authors.affiliation: Division of Inflammation Research, Centre for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Artificial Joints and Biomaterials, Hiroshima University Graduate School of Biomedical Sciences.|Department of Health and Sports Sciences, Mukogawa Women's University, Hyogo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Wakitani
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002678:Chimera; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008592:Menisci, Tibial / Q000473:pathology* / Q000601:surgery; D010227:Parabiosis; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D014945:Wound Healing
chemical_list: D024043:Collagen Type II; D049452:Green Fluorescent Proteins
keywords: green fluorescence protein rat; healing mechanism; meniscus repair; parabiosis; peripheral blood cells; regeneration