微(wei)流控芯(xin)片(pian)為(wei)技術平臺,腫瘤微環境(jing)為(wei)對(dui)象(xiang),在體(ti)外模擬構(gou)建(jian)更(geng)接(jie)近生理(li)條(tiao)件(jian)的腫(zhong)瘤微環境(jing),研(yan)究關(guan)註腫(zhong)瘤(liu)微環境(jing)中(zhong)的主(zhu)要生物(wu)化(hua)學(xue)因(yin)素,特(te)別(bie)是(shi)成纖(xian)維細胞(bao)、間(jian)充(chong)質(zhi)幹細胞(bao)、細胞(bao)外基(ji)質(zhi)以(yi)及(ji)多(duo)種(zhong)生長因(yin)子(zi)在腫(zhong)瘤轉(zhuan)移過(guo)程(cheng)中(zhong)的重(zhong)要作(zuo)用(yong)及(ji)相(xiang)應(ying)生物(wu)學(xue)機(ji)制,分述如下:建(jian)立(li)了壹種(zhong)基(ji)於微(wei)流控芯(xin)片(pian)的異(yi)種(zhong)細胞(bao)間(jian)接接觸(chu)共培(pei)養(yang)的新方(fang)法(fa),用(yong)以(yi)研(yan)究成(cheng)纖(xian)維細胞(bao)和腫(zhong)瘤細胞(bao)之間(jian)的相(xiang)互(hu)作(zuo)用(yong).

        該芯(xin)片(pian)包含(han)多(duo)個細胞(bao)培養(yang)微室和(he)細胞(bao)遷移(yi)區域(yu),能夠(gou)實現無物(wu)理(li)損(sun)傷的細胞(bao)共培(pei)養及(ji)細胞(bao)運動的實(shi)時(shi)監測,並將多(duo)種(zhong)細胞(bao)單(dan)元操(cao)作(zuo)集(ji)成到(dao)壹(yi)個芯(xin)片(pian)上完成.結(jie)果表明,成纖(xian)維細胞(bao)在腫(zhong)瘤細胞(bao)誘(you)導作(zuo)用(yong)下,發生定(ding)向(xiang)遷移運動,同時(shi),成纖(xian)維細胞(bao)受到(dao)活(huo)化(hua)而(er)出現(xian)轉(zhuan)分化(hua)現象(xiang).發(fa)展了壹系列可用於二(er)維和(he)三維細胞(bao)培養(yang)的功(gong)能化(hua)仿生微(wei)流控芯(xin)片(pian),用以(yi)研(yan)究間(jian)充(chong)質(zhi)幹細胞(bao)(MSCs)在涎(xian)腺(xian)腺(xian)樣(yang)囊(nang)性癌(ai)細胞(bao)(ACC-M)微環境(jing)中(zhong)的作(zuo)用(yong),並探討(tao)MSCs與ACC-M發(fa)生相(xiang)互(hu)作(zuo)用(yong)時(shi)可能涉及(ji)的信(xin)號(hao)轉(zhuan)導通(tong)路.基(ji)於此(ci)方(fang)法(fa),能夠(gou)精確實現(xian)細胞(bao)區域(yu)分布及(ji)培(pei)養(yang);可控形成(cheng)可溶因(yin)子(zi)的濃(nong)度梯度;同時(shi)細胞(bao)遷移(yi)分析(xi)可以(yi)定量(liang)化(hua)、實時(shi)化(hua).結果表明1)MSCs受到(dao)ACC-M細胞(bao)的誘(you)導作(zuo)用(yong)發(fa)生細胞(bao)定向(xiang)遷移,這(zhe)壹過(guo)程(cheng)可能是(shi)由ACC-M細胞(bao)分泌(mi)的TGF-β所介導的.2)MSCs會(hui)破壞ACC-M細胞(bao)間(jian)連接(jie),顯著降低(di)其E-cadherin表達,並在CXCL12濃(nong)度梯度作(zuo)用(yong)下,促(cu)進(jin)ACC-M細胞(bao)侵(qin)襲(xi)、轉(zhuan)移,進(jin)壹步揭示(shi)CXCL12/CXCR4信(xin)號(hao)通(tong)路在MSCs促(cu)進(jin)ACC-M轉(zhuan)移過(guo)程(cheng)中(zhong)的重(zhong)要參(can)與作(zuo)用(yong).

        建(jian)立(li)了壹種(zhong)新型(xing)的基(ji)於微(wei)流控芯(xin)片(pian)的細胞(bao)遷移(yi)動力學(xue)監(jian)測方(fang)法(fa),用(yong)以(yi)研(yan)究腫(zhong)瘤細胞(bao)侵(qin)襲(xi)到(dao)三維細胞(bao)外基(ji)質(zhi)的動態(tai)過(guo)程(cheng),並考察(cha)自發侵(qin)襲(xi)過程(cheng)中(zhong)的相(xiang)關(guan)生物(wu)學(xue)行為(wei)變(bian)化(hua).該方法(fa)可對(dui)細胞(bao)運動進(jin)行實時(shi)監測,同(tong)時(shi)能夠(gou)實現對(dui)細胞(bao)運動初(chu)始位(wei)置(zhi)的準(zhun)確定位(wei),可獲取更(geng)多(duo)定量(liang)生物(wu)學(xue)信(xin)息(xi).結(jie)果(guo)表明,腫瘤(liu)細胞(bao)HepG-2在侵(qin)入細胞(bao)外基(ji)質(zhi)的過(guo)程(cheng)中(zhong),通(tong)過與細胞(bao)外基(ji)質(zhi)的相(xiang)互(hu)作(zuo)用(yong),發(fa)生細胞(bao)骨(gu)架重組(zu)和細胞(bao)形態(tai)變(bian)化(hua),促(cu)進(jin)腫瘤(liu)侵(qin)襲(xi)過程(cheng).