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標題: 以坐骨神經損傷為模式探討SDF-1α如何調控人類羊水間葉幹細胞以促進神經再生
Nerve regeneration by intravenous administration of human amniotic fluid mesenchymal stem cells regulated by SDF-1α in a sciatic nerve injury model
作者: 謝獻旭
Hsieh, Hsien-Hsu
關鍵字: 羊水間葉幹細胞;amniotic fluid mesenchymal stem cells;基質衍生因子-1α;第4型趨化因子接受體;stromal derived factor -1α;chemokine receptor type 4
出版社: 生命科學院碩士在職專班
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背景:人類羊水間葉幹細胞(amniotic fluid mesenchymal stem cells:AFS),已經證實可以促進周邊神經再生。在神經受損後會表現基質衍生因子-1α(stromal derived factor 1α:SDF-1α),SDF-1α可以藉由招募前趨細胞(progenitor cells)行使滋養功效(trophic effect)而促進神經細胞的修復。在本篇研究,我們探討在坐骨神經壓傷模式下,以不同時間點靜脈輸注受SDF-1α調節的羊水間葉幹細胞來評估神經修復的可行性。
材料與方法: 63隻Sprague-Dawley大鼠,使用血管夾造成左側坐骨神經壓傷。大鼠隨機分成三組:第一組:壓傷後注射生理食鹽水作為對照組;第二組:壓傷且在受傷後立即靜脈輸注羊水間葉幹細胞(每天給與5x106 cells共3天) (早期給與組);和第三組:壓傷且在受傷第7天時靜脈輸注羊水間葉幹細胞(每天給與5x106 cells共3天) (晚期給與組)。在壓傷後每週評估神經行為、電生理研究、與修復標記(regeneration markers)。同時在不同時間點也評估羊水間葉幹細胞在各器官的分佈與SDF-1α及神經滋養因子(neurotrophic factor)的表現。
結果:在體外實驗藉由Wound healing assays與Transwell migration assay證實SDF-1α能促進羊水間葉幹細胞的移行,且細胞移行能力呈現劑量依賴性。無論是在神經或肌肉壓傷後皆能誘導SDF-1α的表現,且在第10-14天表現達到最高峰。 SDF-1α表現增加時,其受體Chemokine receptor type 4(CXCR-4)也一樣增加。不管在早期或晚期給與組,大部分羊水間葉幹細胞都分佈於肺部。只有在晚期給與組羊水間葉幹細胞明顯地沉積於神經和肌肉。在神經行為、電生理功能、神經組織髓鞘化及神經滋養因子和乙醯膽鹼接受體的表現,晚期給與組改善的程度優於其他兩組。

Background: Human amniotic fluid mesenchymal stem cells (AFS) have been shown to promote peripheral nerve regeneration. The expression of stromal derived factor 1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, we investigated the feasibility of intravenous administration of AFS according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model.
Material and Methods: Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of three groups: Group I: crush injury as the control; Group II: crush injury and intravenous administration of AFS (5x106 cells for 3 days) immediately after injury (early administration); and Group III: crush injury and intravenous administration of AFS (5x106 cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α , neurotrophic factors, and the distribution of AFS in various time profiles were also assessed.
Results: SDF-1α increased the migration and wound healing of AFS in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10-14 days either at nerve or muscle, and this increased expression paralleled the expression of its receptor CXCR-4. Most AFS was distributed to the lung during early or late administration. Significant deposition of AFS in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group.
Conclusion: AFS cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFS paralleled the expression profiles of SDF-1α and its receptor CXCR-4 either in muscle or nerve. AFS administration led to improvements of neurobehavior and expression of regeneration markers. Intravenous administration of AFS may be a promising alternative treatment strategy in peripheral nerve disorder.
其他識別: U0005-0607201213245300
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