| 特集名 | 骨の再生医学 | |
|---|---|---|
| 題名 | 間葉系幹細胞の基礎 (1) 間葉系幹細胞の骨分化カスケード | |
| 発刊年月 | 2006年 10月 | |
| 著者 | 土肥 祥子 | 奈良県立医科大学健康政策医学講座 |
| 【 要旨 】 | 骨髄中にわずかに存在する間葉系幹細胞を増殖し，さらにデキサメタゾン，アスコルビン酸およびβ-グリセロフォスフェイトを含む骨誘導培地で培養するとシャーレ上に石灰化骨組織を再構築できる．最近，患者自身の骨髄細胞より骨分化カスケードを経て多孔体セラミック上に作製されたこの再生培養骨を骨修復の治療に活用できるようになった．間葉系幹細胞から再構築された骨組織までの骨分化カスケードにおけるステージごとの細胞とマトリックスの変化を，骨形成の指標となるさまざまな転写因子や基質蛋白質の発現で検証できる．さらに骨分化カスケードの最終段階である基質石灰化の三次元像による解析が試みられ，細胞と石灰化骨基質から構築された培養骨の高次構造が示されている． | |
| Theme | Bone tissue regeneration | |
|---|---|---|
| Title | An osteogenic differentiation cascade of mesenchymal stem cells | |
| Author | Yoshiko Dohi | Department of Public Health Policy, Nara Medical University School of Medicine |
| [ Summary ] | Bone marrow contains pluripotent stem cells of the adipocytic, chondrocytic, and osteoblastic cell lineages. In vitro proliferated marrow mesenchymal stem cells (MSCs) can further differentiate into bone forming osteoblasts. They formed mineralized nodules, when subcultured in the presence of dexamethasone, ascorbic acid, and β-glycerophosphate. Using a two-step tissue engineering technique, ex vivo fabricated osteoblast / biomaterials aid in therapy for hard tissue repair, once materials are coated with bone matrix by osteoblasts derived from patients' MSCs. MSC-derived osteoblasts progress through a three stage process of differentiation : proliferation, matrix production, and mineralization. These differentiation and bone formation processes are largely mediated by various cytokines such as BMP-2, transcriptional factors, Cbfa1 and osterix, neighboring mature cells, along with extracellular matrix proteins, whose expression is strictly controlled both spatially and temporally. The bone matrix is composed primarily of type I collagen, which forms an extracellular matrix for the deposition of hydroxyapatite, and non-collagenous proteins. Cellular mRNA levels of alkaline phosphatase (ALP), osteopontin and osteocalcin increased concomitantly with the development of bone nodules. Computer assisted confocal laser scanning microscopy analysis showed in vitro bone tissue consisting of layers of mineralized matrix with round cells in the matrix lacunae, osteoid, and osteoblasts on the osteoid surface. |
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