title: In-advance trans-medullary stimulation of bone marrow enhances spontaneous repair of full-thickness articular cartilage defects in rabbits.
abstract: Mesenchymal stromal cells (MSCs), especially those lying close to cartilage defects, are an important cell source for cartilage regeneration. We hypothesize that a larger number of MSCs might become available, if the bone marrow in the immediate vicinity of the subchondral bone is stimulated for MSCs in advance of the creation of cartilage defects. A trans-medullary passage-way reaching the immediate vicinity of the subchondral bone was created 4 days prior to the creation of cartilage defects. In another setting, basic fibroblast growth factor (bFGF) was administered through the trans-medullary passage-way in order to augment the stimulation of MSCs. The rabbits were killed at various times after the creation of cartilage defects. Triple staining of bromodeoxyuridine (BrdU), CD44 and CD45 and histological evaluation were subsequently performed. A considerable proportion of the proliferating cells were identified as bone-marrow-derived MSCs. Enumeration of BrdU-positive cells demonstrated that trans-medullary stimulation, especially with bFGF, increased the number of proliferating cells. The histological grading score of trans-medullary stimulation with bFGF group was superior to that of the other groups. Thus, in-advance stimulation of the bone marrow effectively increases the number of proliferating cells. The putative progenitor cells for chondrocytes stimulated thereby are likely to be recruited to the osteochondral defects at the appropriate time, contributing to the repair of full-thickness articular cartilage defects at the early follow-up time point.
authors.affiliation: Department of Orthopaedic Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. grotto@belle.shiga-med.ac.jp
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nishizawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Imai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mimura
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Kubo
authors.forename: Susumu
authors.initials: S
authors.lastname: Araki
authors.forename: Suguru
authors.initials: S
authors.lastname: Shioji
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takemura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsusue
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D002357:Cartilage Diseases / Q000473:pathology / Q000534:rehabilitation / Q000628:therapy*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D048091:Guided Tissue Regeneration / Q000379:methods*; D015552:Injections, Intralesional; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D010812:Physical Stimulation / Q000379:methods; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D012075:Remission, Spontaneous; D013268:Stimulation, Chemical; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D016222:Fibroblast Growth Factor 2