低能量光照結合間葉幹細胞移植對骨質疏鬆大鼠之影響探討

骨髓間葉幹細胞 (Mesenchymal stem cells, MSCs) 具有自我更新及多向性分化能力。先前研究結果顯示紅光及近紅光低能量光照 (Low level light irradiation, LLLI) 可提升大鼠骨髓 MSCs 的增生、硬骨分化及細胞遷移能力。本研究目的在進一步探討植入經過 LLLI 處理的 MSCs 對骨質疏鬆症大鼠的影響。首先以地塞米松誘發大鼠產生骨質疏鬆症，並分別分析正常組與骨質疏鬆症大鼠的 MSCs 增生與硬骨分化能力的表現。再將正常的骨髓 MSCs 以螢光標記，利用紅光與近紅光 LLLI 處理後移植至骨質疏鬆症大鼠身上，以活體影像系統 (In vivo imaging system, IVIS) 觀察細胞遷移情況，並利用微電腦斷層造影 (Micro computed tomography, Micro-CT) 量測骨密度、骨小樑厚度、骨小樑數量與骨小樑分散度。結果發現，骨質疏鬆症大鼠的 MSCs 在增生能力上表現比正常大鼠的 MSCs 差，而硬骨分化能力則較好。將 MSCs 以 LLLI 處理後移植至骨質疏鬆症大鼠體內，IVIS 影像觀察到經過紅光刺激的 MSCs 遷移至骨髓的含量較多。Micro CT 發現經過紅光刺激的組別其骨質含量有明顯的上升。而治療後大鼠骨髓 MSCs 的增生能力與硬骨分化能力也以紅光刺激的組別較佳。綜合以上結果，紅光刺激能有效提升骨髓 MSCs 的遷移能力並有恢復骨質疏鬆症大鼠骨質的效果。

關鍵字

骨質疏鬆症；骨髓間葉幹細胞；紅光；近紅光；低能量光照

並列摘要

Mesenchymal stem cells (MSCs) have the capabilities of self-renewal and multi-lineage differentiation. Previously, we have demonstrated the beneficial effect of low level light irradiation (LLLI) using red and near-infrared (NIR) light on the proliferation, osteogensis and migration of rat MSCs. The purpose of the study was to investigate the effect of transplantation of LLLI-treated MSCs into the osteoporotic rats. First of all, osteoporosis in rats was induced by subcutaneous injection of dexamethasone. Proliferation and osteogenic differentiation of MSCs derived from normal and osteoporotic rats were analyze. Normal MSCs were labeled with fluorescence and subjected to red and NIR LLLI prior to intravenous injection to osteoporosis rats. MSCs migration was observed by In vivo imaging system (IVIS). Bone density, trabecular thickness, trabecular number and trabecular bone dispersity of osteoporotic rats were determined by Micro-computer tomography (Micro-CT). It was found that MSCs derived from osteoporosis rats had lower proliferation but better osteogenic differentiation than normal MSCs. IVIS images showed increased MSCs migration in bone marrow in the red LLLI group. Micro-CT found that red LLLI group had higher bone mass. Proliferation and osteogenic differentiation of MSCs derived from red LLLI group were also better. In conclusion, red LLLI can effectively enhance bone marrow MSCs migration and help recovery of bone mass in osteoporotic rats.

並列關鍵字

osteoporosis ； mesenchymal stem cell ； red light ； near infrared light ； low level light irradiation

參考文獻

[1] Huang Y-Y, Sharma SK, Carroll J, Hamblin MR. Biphasic Dose Response in Low Level Light Therapy – An Update. Dose Response. 2011;9:602-18.

[2] Caplan AI, Bruder SP. Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med. 2001;7:259-64.

[3] Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 2004;40:1275-84.

[4] Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res. 2002;69:908-17.

[5] Marie PJ, Kassem M. Osteoblasts in osteoporosis: past, emerging, and future anabolic targets. Eur J Endocrinol. 2011;165:1-10.

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低能量光照結合間葉幹細胞移植對骨質疏鬆大鼠之影響探討

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