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幹細胞和生物醫材對股骨大缺損組織修復/再生之效果及可能細胞機轉的研究

Effects and Possible Mechanisms of Stem Cells and Biomaterials on Repair/Regeneration of Critical-sized Femora Bone Defects

摘要


年齡增長後,骨髓中間葉幹細胞數量明顯減少。另外,年齡增長後骨折癒合有明顯延遲情形,骨髓細胞骨生成能力和骨生成細胞增生明顯降低。 到目前為止有關利用骨髓幹細胞配合生物醫材對年齡增長後不癒合骨大缺損之修復後骨組織修復及其細胞分子機轉仍然有限(但卻相當重要及值得去探討的)。 本研究旨在利用骨髓細胞體外骨生成模式,自成年大白鼠長骨中取出的骨髓細胞,經Ficoll-Paque比重梯度分離法所獲得富含間葉(或骨)幹細胞之骨髓細胞進行細胞培養,並利用細胞標記(CD marker)分離出間葉幹細胞,將此骨髓間葉幹細胞和生醫材料植入鼠齡為12月之大白鼠骨大缺損處,2月後利用骨組織形態學分析等方法評估骨髓間葉幹細胞和生醫材料並用防治年齡增長導致後骨大缺損癒合(骨再生)的效果及可能的機轉。實驗結果發現在誘導因子處理後,可見造骨細胞分化、礦物化骨群體形成情形。由骨組織形態學動態和靜態參數得知,幹細胞和生物醫材組骨量、單位長度和面積造骨細胞數目、骨生成速率和礦物化沈積速率均明顯增加。因此,本研究結果顯示間葉幹細胞配合生物醫材有效地增進骨大缺損之修復。

並列摘要


With aging, the decrease in bone mass (or hone mineral density) could increase the occurrence of fracture. Thus, a decrease in personal hone mineral density could increase the occurrence of fracture during military practice or exercise. A fracture could result in loss of function or even death. Therefore, investigation on keeping hone tissue and cells functionally and prevention of damage of hone structure are imperative in sport medicine. With aging, dramatic bone loss and significant decreases in hone formation are noted. Shih found that there are significant decreases in proliferation and differentiation of osteo-progenitors cell and osteoblastic function with aging. Recent evidences revealed that there are significant decreases in hone marrow messenchymal stem cells (MSCs) and bone healing with aging. Therefore, MSCs may play an important role in critical size defect healing. Therefore, the purpose of this study was to investigate effects of transplantation of bone marrow stem cells and tissue engineering on nonunion large hone defect repair (regeneration) and evaluation of its therapeutic potential by microradiography and bone histomorphometry. Appearance of cuboid-shaped osteoblastic cells, unmineralized, and mineralized colonies were noted after osteogenic induction. Bone micro-radiographic analysis showed radiopaque area (area of mineralization) began to appear 2 months in biomaterials with MSCs group or 2 months in MSCs alone group while no evidence of bone formation in control or biomaterials group even 2 months after implantation.

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