后腿膝蓋部髕肌腱斷裂的小白鼠，通過植入從胚胎干細胞分階段分化而來的肌腱后,，又恢復(fù)了正常的活動能力,。浙江大學(xué)醫(yī)學(xué)院歐陽宏偉教授帶領(lǐng)課題組完成的這項研究成果，為應(yīng)用胚胎干細胞治療肌腱等軟組織損傷提出了一條現(xiàn)實的實現(xiàn)途徑,。相關(guān)論文近日發(fā)表在《干細胞》(STEM CELLS)上,。這是國際上第一篇關(guān)于利用胚胎干細胞培養(yǎng)肌腱進行修復(fù)再生的研究論文，雜志評審專家認為是具有開拓性的新穎研究,。
歐陽教授的課題組將10—20個胚胎干細胞小團塊“鋪”在處理過的培養(yǎng)板上進行低密度培養(yǎng),，通過篩選，將化成間質(zhì)干細胞的克隆干細胞“收集”起來,，再進行進一步克隆篩選,、擴增和定性。這些分化后的間質(zhì)干細胞在特殊培養(yǎng)液中浸泡兩個星期后,，形成膜狀的間質(zhì)干細胞片,，可被卷成肌腱的形狀，再經(jīng)過一段時間的牽拉,、擠壓的刺激,，就能分化成肌腱細胞正常“工作”。
肩,、膝,、肘等關(guān)節(jié)部位的肌腱、韌帶等結(jié)締組織損傷越來越多（占運動損傷的50%）,。有數(shù)據(jù)表明,，每2億人口中一年至少有上千萬的肌腱損傷病例。目前對肌腱損傷的臨床治療手段如理療和手術(shù)縫合等,，療效有限,，且因為肌腱不具備完全再生能力，所以肌腱損傷后組織修復(fù)的結(jié)構(gòu)和力學(xué)性能低下,，常重復(fù)斷裂,，影響了病人的生活工作質(zhì)量和終止了許多年輕運動員的職業(yè)生命,。組織工程技術(shù)和干細胞技術(shù)的不斷成熟為提高肌腱的修復(fù)質(zhì)量帶來新的機會。
美國賓夕法尼亞大學(xué)研究組報告胚胎肌腱細胞具有完全再生能力,，而成體肌腱細胞卻沒有,。胚胎干細胞具有發(fā)育的全能性，能分化出成體動物的所有組織和器官,，歐陽宏偉稱之為“百變天后”,，所以它是最理想的胚胎源性再生細胞材料。在2009年美國FDA批準Geron公司進行世界上第一例胚胎干細胞臨床實驗研究治療神經(jīng)組織病變之前,，醫(yī)學(xué)界尚未有人通過胚胎干細胞進行體外培植后植入修復(fù)組織,，主要的擔(dān)心是這位“百變天后”的分化能力太強，可控性不高,。歐陽宏偉教授采用了分步誘導(dǎo)等新思路和新技術(shù),，大大降低了常規(guī)實驗中因胚胎干細胞分化不全而導(dǎo)致腫瘤形成的風(fēng)險，實驗涉及的所有小白鼠都未發(fā)生腫瘤,，而肌腱再生質(zhì)量卻大大提高,。雜志社評委認為，這個成果為推進胚胎干細胞走向應(yīng)用,，用于臨床再生結(jié)締組織提供了實驗依據(jù)和新穎的思路,。
歐陽教授長期從事細胞移植的再生組織器官技術(shù)研究，此前他已實現(xiàn)從骨髓中分離出間質(zhì)干細胞進行肌腱體外培養(yǎng)再植,，而這次是通過胚胎干細胞體外培養(yǎng)再植,。歐陽教授介紹說,，胚胎干細胞的生長能力和生物特性均優(yōu)于骨髓間質(zhì)干細胞,，更適用于大批量的培養(yǎng)，在臨床應(yīng)用方面具有更廣闊的前景,。
胚胎干細胞是人體發(fā)展的初始階段,，胚胎干細胞被認為是治療修復(fù)人體的最好材料。美國奧巴馬總統(tǒng)上任后的第一個科技政策就是支持鼓勵胚胎干細胞研究,，并認為干細胞研究會影響美國以后的國家戰(zhàn)略地位,。干細胞產(chǎn)業(yè)被李嘉誠先生認為是繼信息產(chǎn)業(yè)后下一個戰(zhàn)略產(chǎn)業(yè)，美國的Osiri干細胞公司被認為是美國的下一個“微軟”,。目前走向臨床應(yīng)用的主要是成體干細胞,，隨著干細胞生物學(xué)知識和干細胞技術(shù)不斷成熟，胚胎干細胞也將根據(jù)不同組織器官的研究成熟度不同而分步有序地走向臨床應(yīng)用,，并將極大地促進臨床醫(yī)學(xué)發(fā)展,。（生物谷Bioon.com）
生物谷推薦原始出處：
STEM CELLS 12 Mar 2009 DOI:10.1002/stem.61
Stepwise Differentiation of Human Embryonic Stem Cells Promotes Tendon Regeneration by Secreting Fetal Tendon Matrix and Differentiation Factors
Xiao Chen 1, Xing-Hui Song 1, Zi Yin 1, Xiao-Hui Zou 2, Lin-Lin Wang 1, Hu Hu 3, Tong Cao 4, Minghao Zheng 5, Hong Wei Ouyang 1 6 *§
1Center for Stem Cells and Tissue Engineering, Zhejiang University School of Medicine, Hangzhou, China
2Womens Hospital, Zhejiang University School of Medicine, Hangzhou, China
3Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
4Stem Cell Laboratory, Faculty of Dentistry, National University of Singapore, Singapore
5Centre for Orthopaedic Research, School of Surgery and Pathology, University of Western Australia, Perth; Australia Perth Bone and Tissue Bank, Nedlands, Australia
6Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Human embryonic stem cells (hESCs) are ideal seed cells for tissue regeneration, but no research has yet been reported concerning their potential for tendon regeneration. This study investigated the strategy and efficacy of using hESCs for tendon regeneration as well as the mechanism involved.
hESCs were first induced to differentiate into mesenchymal stem cells (MSCs), which had the potential to differentiate into the three mesenchymal lineages and were positive for MSC surface markers. hESC-derived MSCs (hESC-MSCs) regenerated tendon tissues in both an in vitro tissue engineering model and an in vivo ectopic tendon regeneration model, as confirmed by the expression of tendon-specific genes and structure. In in-situ rat patellar tendon repair, tendon treated with hESC-MSCs had much better structural and mechanical properties than controls. Further, hESC-MSCs remained viable at the tendon wound site for at least 4 weeks and secreted human fetal tendon-specific matrix components and differentiation factors, which then activated the endogenous regeneration process in tendon. Moreover, no teratoma was found in any samples.
These findings demonstrate a safe and practical strategy of applying ESCs for tendon regeneration and may assist in future strategies to treat tendon diseases.
