游思維

成年哺乳動(dòng)物發(fā)育和再生的嗅神經(jīng)能夠進(jìn)入嗅球，在中樞神經(jīng)系統(tǒng)微環(huán)境中生長并與靶細(xì)胞建立突觸聯(lián)系。嗅球之所以有別于其他中樞神經(jīng)系統(tǒng)組織，具有終身支持嗅神經(jīng)再生的能力，就在于嗅黏膜、嗅神經(jīng)和嗅球中廣泛分布的嗅鞘細(xì)胞（olfactory ensheathing cells）。嗅鞘細(xì)胞是一種其前體細(xì)胞位于嗅黏膜內(nèi)的特殊大膠質(zhì)細(xì)胞，在發(fā)育、形態(tài)和免疫細(xì)胞化學(xué)等諸多方面，與其他類型膠質(zhì)細(xì)胞截然不同。嗅鞘細(xì)胞兼具雪旺細(xì)胞和星形膠質(zhì)細(xì)胞的特性，能構(gòu)成嗅神經(jīng)鞘膜包繞嗅神經(jīng)元的軸突，自周圍神經(jīng)系統(tǒng)主動(dòng)遷移進(jìn)入嗅球并與其自然整合。嗅鞘細(xì)胞還可分泌多種神經(jīng)營養(yǎng)因子，表達(dá)不同親和性的神經(jīng)營養(yǎng)因子受體，分泌軸突再生所必需的細(xì)胞外基質(zhì)和細(xì)胞黏附分子。嗅鞘細(xì)胞具有以上優(yōu)點(diǎn)，近20年來已成為中樞神經(jīng)損傷后細(xì)胞移植修復(fù)理論及應(yīng)用基礎(chǔ)研究領(lǐng)域的熱點(diǎn)，并不斷取得進(jìn)展和突破。嗅鞘細(xì)胞已成為可供中樞神經(jīng)系統(tǒng)損傷后細(xì)胞移植治療的重要備選細(xì)胞之一。

一、嗅鞘細(xì)胞的起源與特征

胚胎發(fā)育時(shí)期，嗅鞘細(xì)胞直接起源于外胚層的鼻板，有別于星形膠質(zhì)細(xì)胞、少突膠質(zhì)細(xì)胞等起源于腦泡的中樞神經(jīng)系統(tǒng)膠質(zhì)細(xì)胞。嗅鞘細(xì)胞廣泛分布于嗅黏膜、嗅神經(jīng)和嗅球的表面兩層（嗅神經(jīng)纖維層和嗅小球?qū)樱?，其在體內(nèi)、外的形態(tài)學(xué)特征，也不同于其他類型的膠質(zhì)細(xì)胞。因此，不能將嗅鞘細(xì)胞混同于任何其它周圍神經(jīng)系統(tǒng)和中樞神經(jīng)系統(tǒng)的膠質(zhì)細(xì)胞。

不同發(fā)育和生長階段的嗅鞘細(xì)胞的形態(tài)均具有特征。發(fā)育中的嗅鞘前體細(xì)胞因其深色外表、與軸突的聯(lián)系方式及電鏡形態(tài)而有別于其他遷移細(xì)胞。遷移嗅鞘細(xì)胞有長、圓形兩種。前者發(fā)出纖細(xì)的層狀突起包裹小的軸突束，被認(rèn)為是“成熟”嗅鞘細(xì)胞；后者最大可能是嗅鞘前體細(xì)胞，其后分化為成熟嗅鞘細(xì)胞。成年動(dòng)物嗅球內(nèi)的嗅鞘細(xì)胞僅在形成膠質(zhì)細(xì)胞外限制膜的區(qū)域與基板接觸，這點(diǎn)不同于雪旺細(xì)胞，卻類似于星形膠質(zhì)細(xì)胞。同其他周圍神經(jīng)系統(tǒng)-中樞神經(jīng)系統(tǒng)移行區(qū)相比，嗅鞘細(xì)胞和星形膠質(zhì)細(xì)胞的漿膜并未被基底膜所阻隔。嗅鞘細(xì)胞也可在血管處形成終鈕。供體動(dòng)物年齡和培養(yǎng)條件的差異，可使體外培養(yǎng)的嗅鞘細(xì)胞形態(tài)相去甚遠(yuǎn)。原代培養(yǎng)成年大鼠嗅球的表面兩層，可獲得三種不同形態(tài)的細(xì)胞：梭形細(xì)胞、扁圓形細(xì)胞和有突起的多極細(xì)胞。梭形細(xì)胞被認(rèn)為是毛細(xì)血管內(nèi)皮細(xì)胞，扁圓形細(xì)胞為小膠質(zhì)細(xì)胞，多突起細(xì)胞符合嗅鞘細(xì)胞的表型和功能標(biāo)準(zhǔn)，因此被確定為嗅鞘細(xì)胞。根據(jù)免疫親和原理，可用抗低親和性神經(jīng)營養(yǎng)素受體p75抗體將嗅鞘細(xì)胞從其他取自嗅球的培養(yǎng)細(xì)胞純化出來。

嗅鞘細(xì)胞在發(fā)育和成年期均可包裹生長或損傷修復(fù)中的嗅神經(jīng)纖維，為其提供適宜的生長環(huán)境。這一獨(dú)特作用，有其獨(dú)特的表型基礎(chǔ)。Vimentin是一種主要在中樞神經(jīng)系統(tǒng)發(fā)育階段表達(dá)的蛋白質(zhì)，是成年動(dòng)物嗅鞘細(xì)胞中間絲的主要成分，表明嗅鞘細(xì)胞保留了未成熟的表型，因而具有促進(jìn)軸突生長的特性。嗅鞘細(xì)胞能夠分泌多種促進(jìn)神經(jīng)元存活和軸突再生所必需的細(xì)胞外基質(zhì)和細(xì)胞黏連分子（如L1、層黏連蛋白、纖維連接蛋白和神經(jīng)細(xì)胞黏附分子等）神經(jīng)營養(yǎng)因子并表達(dá)不同親和性的神經(jīng)營養(yǎng)因子受體，在中樞神經(jīng)系統(tǒng)內(nèi)提供了適宜軸突生長再生的環(huán)境。嗅鞘細(xì)胞還能夠產(chǎn)生血小板源性生長因子、神經(jīng)肽Y和S100，這些因子都是已知的促進(jìn)神經(jīng)細(xì)胞生長和存活的因子。

二、嗅鞘細(xì)胞移植修復(fù)中樞神經(jīng)系統(tǒng)損傷的研究進(jìn)展

成年動(dòng)物嗅覺系統(tǒng)和嗅鞘細(xì)胞保留了許多發(fā)育階段的特性和可塑性，因此植入異體中樞神經(jīng)系統(tǒng)的嗅鞘細(xì)胞具有隨再生軸突遷移并促進(jìn)軸突再生的能力。盡管其他膠質(zhì)細(xì)胞已被用于促進(jìn)成年中樞神經(jīng)系統(tǒng)的修復(fù)，但嗅鞘細(xì)胞似乎為更佳選擇。嗅鞘細(xì)胞在正常情況下存在于中樞神經(jīng)系統(tǒng)，與中樞神經(jīng)系統(tǒng)的整合及在其內(nèi)部的遷移是自然的，也就使得嗅鞘細(xì)胞所形成的支架橋梁，能夠穿越再生軸突無法逾越的膠質(zhì)瘢痕。與星形膠質(zhì)細(xì)胞及雪旺細(xì)胞相比，嗅鞘細(xì)胞可成功與宿主成年中樞神經(jīng)系統(tǒng)實(shí)質(zhì)整合，并伴隨再生軸突向特定的靶組織遷移。近年來，嗅鞘細(xì)胞不斷被用于中樞神經(jīng)系統(tǒng)尤其是脊髓損傷修復(fù)的研究。

1.嗅鞘細(xì)胞對(duì)脊髓損傷修復(fù)的作用：嗅鞘細(xì)胞促進(jìn)中樞神經(jīng)系統(tǒng)再生的研究始于1994年。Ramon-Cueto等[1]首次將純化的嗅鞘細(xì)胞植入異體成年大鼠脊髓胸10節(jié)段背根神經(jīng)進(jìn)入脊髓處，發(fā)現(xiàn)被切斷的背根神經(jīng)可再生進(jìn)入成年大鼠脊髓，伴隨嗅鞘細(xì)胞穿過脊髓后外側(cè)束和背根與脊髓移行區(qū)的膠質(zhì)瘢痕，進(jìn)入雙側(cè)脊髓第Ⅰ、Ⅱ、Ⅲ板層。一些傳入纖維穿行于第Ⅳ、Ⅴ板層內(nèi)側(cè)，并經(jīng)灰連合背側(cè)到達(dá)對(duì)側(cè)后角，部分再生軸突可抵達(dá)對(duì)側(cè)后角第Ⅲ、Ⅳ板層。盡管僅有少量纖維長入后索，但再生的感覺纖維并不進(jìn)入前索，所有這些軸突都進(jìn)入在正常情況下應(yīng)該抵達(dá)的板層。鑒于移植的嗅鞘細(xì)胞和再生軸突位于同一部位，且再生纖維不進(jìn)入在正常情況下并不支配的區(qū)域，作者認(rèn)為軸突沿特定途徑再生，嗅鞘細(xì)胞伴隨再生軸突并為其生長提供適宜的環(huán)境。

李英和Raisman等[2-3]在其前期形態(tài)學(xué)研究的基礎(chǔ)上，以電極破壞成年大鼠一側(cè)頸髓皮質(zhì)脊髓束，將取自成年大鼠嗅球原代培養(yǎng)未經(jīng)純化的嗅鞘細(xì)胞（含小膠質(zhì)細(xì)胞和血管內(nèi)皮細(xì)胞）植入損傷區(qū)。術(shù)后1周損傷纖維出現(xiàn)纖細(xì)、有小分支的枝芽，并依附嗅鞘細(xì)胞沿皮質(zhì)脊髓束向尾側(cè)方向延伸。這些再生神經(jīng)纖維于術(shù)后3周聚集成束，穿越損傷區(qū)域全長，進(jìn)入皮質(zhì)脊髓束的尾側(cè)段，并首次取得大鼠脊髓損傷后截癱肢體運(yùn)動(dòng)功能恢復(fù)的重大突破。此項(xiàng)研究于1997年發(fā)表于《Science》，并被該雜志評(píng)為當(dāng)年十大科技進(jìn)展之一。他們進(jìn)一步的研究觀察到，移植入的嗅鞘細(xì)胞分兩種主要類型：一種是表達(dá)p75的S細(xì)胞，另一種為表達(dá)纖維連接蛋白的A細(xì)胞。前者包繞單一軸突形成典型一對(duì)一方式的周圍神經(jīng)髓鞘，后者則聚集為管狀鞘膜包裹成束的纖維，當(dāng)再生纖維重返中樞神經(jīng)系統(tǒng)微環(huán)境時(shí)被少突膠質(zhì)細(xì)胞所包裹。因此，嗅鞘細(xì)胞的主要作用被認(rèn)為是為受損中樞神經(jīng)纖維提供跨越損傷區(qū)域的橋梁[4]。

李英和Raisman的研究僅選擇性損傷了一側(cè)皮質(zhì)脊髓束，Ramon-Cueto等[5]則將嗅鞘細(xì)胞移植用于脊髓全橫斷損傷后的修復(fù)。他們在完全離斷的脊髓斷端間置入充滿雪旺細(xì)胞的引導(dǎo)管，然后采用立體定向技術(shù)，在兩斷端脊髓實(shí)質(zhì)內(nèi)經(jīng)微玻管注入純化的成年大鼠嗅球原代培養(yǎng)的嗅鞘細(xì)胞懸液。大量紅核脊髓束和上行脊髓固有神經(jīng)的再生纖維與嗅鞘細(xì)胞并行，穿越膠質(zhì)瘢痕后經(jīng)引導(dǎo)管進(jìn)入損傷區(qū)對(duì)側(cè)的脊髓組織內(nèi)，并在白質(zhì)和灰質(zhì)中與植入的嗅鞘細(xì)胞并行長距離延伸。在其后的研究中，Ramon-Cueto等[6]研究的是全橫斷脊髓后不再應(yīng)用雪旺細(xì)胞引導(dǎo)管，而只將嗅鞘細(xì)胞懸液植入脊髓斷端內(nèi)。所有接受嗅鞘細(xì)胞移植的大鼠均于術(shù)后3～7月恢復(fù)了截癱后肢支撐體重和自主運(yùn)動(dòng)的功能，并出現(xiàn)對(duì)輕觸覺和本體覺刺激的反射活動(dòng)。

應(yīng)用嗅鞘細(xì)胞脊髓內(nèi)移植在短短3年時(shí)間內(nèi)連續(xù)獲得截癱大鼠肢體運(yùn)動(dòng)功能的恢復(fù)，使科學(xué)家們極為振奮，不斷努力將嗅鞘細(xì)胞移植作為攻克創(chuàng)傷性截癱的第二代療法。然而，隨著嗅鞘細(xì)胞研究的不斷深入，也出現(xiàn)了部分相左的意見?？v觀十多年的文獻(xiàn)，絕大多數(shù)的研究是肯定嗅鞘細(xì)胞移植具有促進(jìn)脊髓修復(fù)作用：（1）能夠促進(jìn)動(dòng)物行走、姿勢和呼吸運(yùn)動(dòng)功能的恢復(fù)。多項(xiàng)來自不同實(shí)驗(yàn)室的研究指出，將嗅鞘細(xì)胞植入急性和慢性損傷的脊髓內(nèi)，可獲得截癱后肢運(yùn)動(dòng)功能的部分恢復(fù)[7-18]。轉(zhuǎn)染膠質(zhì)細(xì)胞源性神經(jīng)營養(yǎng)因子（glial cell-derived neurotrophic factor, GDNF）和神經(jīng)營養(yǎng)素-3（neurotropin-3,NT-3）的嗅鞘細(xì)胞[19-20]，或嗅鞘細(xì)胞與FK506、COX-2、NOS拮抗劑、富含多巴胺神經(jīng)元的腹側(cè)中腦組織及神經(jīng)干細(xì)胞等聯(lián)合應(yīng)用[21-24]，可發(fā)揮更為顯著的修復(fù)效果。將取自外層嗅球或鼻黏膜的嗅鞘細(xì)胞制成懸液植于動(dòng)物半橫斷或挫傷的上段頸髓中，脊髓控制呼吸的功能得以部分恢復(fù)[25-26]。自體鼻腔嗅黏膜固有層內(nèi)富含嗅鞘細(xì)胞，取材便利，移植后無免疫排斥[26-28]，因而有著更好的治療脊髓損傷的臨床應(yīng)用前景；（2）植入脊髓后具有增殖和遷移能力。嗅鞘細(xì)胞能與宿主中樞神經(jīng)系統(tǒng)實(shí)質(zhì)整合，在損傷區(qū)兩側(cè)遷移，穿越軸突無法逾越的空洞和膠質(zhì)瘢痕，形成供再生軸突依附、延伸的橋梁。移植的嗅鞘細(xì)胞主要有表達(dá)p75的S細(xì)胞和表達(dá)纖維粘附素的A細(xì)胞。前者包繞單一軸突形成典型一對(duì)一方式的周圍神經(jīng)髓鞘，后者則聚集為管狀鞘膜包裹成束的纖維，當(dāng)再生纖維進(jìn)入脊髓時(shí)，再次被寡突膠質(zhì)細(xì)胞所包裹，因此嗅鞘細(xì)胞主要作用被認(rèn)為是為受損軸突提供跨越損傷區(qū)域的橋梁[19,29-31]；（3）促進(jìn)并伴隨軸突向特定靶組織的長距離再生[10,13-15,32-33]。嗅鞘細(xì)胞還可包繞脫髓鞘的軸突使其重新髓鞘化[34]，并提高動(dòng)作電位的傳導(dǎo)速度；（4）減輕炎癥反應(yīng)、組織和細(xì)胞構(gòu)筑的破壞和膠質(zhì)瘢痕[5,17,33]；（5）能夠促進(jìn)脊髓損傷后大腦皮質(zhì)和腦干下行神經(jīng)元的存活[35]。

部分研究也有不同的發(fā)現(xiàn)：(1)單獨(dú)使用嗅鞘細(xì)胞不能促進(jìn)脊髓功能的恢復(fù)，或雖有功能恢復(fù)但非嗅鞘細(xì)胞的直接作用[36-39]。Barnett和 Riddell[39]通過文獻(xiàn)回顧，綜合分析了既往動(dòng)物實(shí)驗(yàn)的證據(jù)和功能恢復(fù)的可能機(jī)理，認(rèn)為嗅鞘細(xì)胞在植入不同類型的損傷脊髓中是能夠促進(jìn)功能恢復(fù)的，但相應(yīng)的組織學(xué)證據(jù)卻表明，軸突雖然可在植入的嗅鞘細(xì)胞范圍內(nèi)再生，但不能穿越損傷區(qū)或與對(duì)側(cè)的神經(jīng)元重新連接。因此功能恢復(fù)的原因可能是嗅鞘細(xì)胞的神經(jīng)保護(hù)作用以及未損傷神經(jīng)纖維的代償性發(fā)芽；(2)嗅鞘細(xì)胞植入脊髓后不具備獨(dú)特的遷移能力，也不能橋接損傷的脊髓傳導(dǎo)束[40]。外源性嗅鞘細(xì)胞只能在周圍神經(jīng)中遷移而不能進(jìn)入中樞神經(jīng)系統(tǒng)；(3)不支持軸突再生或再生異常[40]，不能使軸突再髓鞘化[41]。上行和下行長束軸突并未優(yōu)先向嗅鞘細(xì)胞條索內(nèi)延伸生長[40]。嗅鞘細(xì)胞對(duì)傳入神經(jīng)纖維的再生作用極為有限，嗅鞘細(xì)胞與軸突的重新長入和功能性神經(jīng)纖維的連接重建并無直接關(guān)聯(lián)。

早期研究通常移植體外培養(yǎng)的純化嗅鞘細(xì)胞，但近期研究顯示高純度嗅鞘細(xì)胞的效果并不一定優(yōu)于低純度的細(xì)胞。在多數(shù)研究中，嗅鞘細(xì)胞的移植時(shí)機(jī)選擇在脊髓損傷后的急性期。但由于脊髓繼發(fā)性損傷可能會(huì)對(duì)移植細(xì)胞的活性造成程度不同的損害，因此在脊髓損傷急性期過后移植嗅鞘細(xì)胞，可能較損傷后立即移植細(xì)胞有著更好的效果。

2.嗅鞘細(xì)胞對(duì)視神經(jīng)損傷修復(fù)的作用：視網(wǎng)膜與視神經(jīng)在組織學(xué)上隸屬中樞神經(jīng)系統(tǒng)，其軸突組成視神經(jīng)的視網(wǎng)膜神經(jīng)節(jié)細(xì)胞（簡稱節(jié)細(xì)胞）屬中樞神經(jīng)元。由于全視網(wǎng)膜平鋪技術(shù)便于研究分析整個(gè)視網(wǎng)膜中的節(jié)細(xì)胞，節(jié)細(xì)胞的胞體和有髓軸突可以分開處理，視網(wǎng)膜和視神經(jīng)已成為廣泛應(yīng)用于中樞神經(jīng)損傷修復(fù)研究方便而實(shí)用的模型。

武明媚等[42]將嗅鞘細(xì)胞植入球后切斷的視神經(jīng)眶側(cè)殘段內(nèi)，在術(shù)后2、7和14 d三個(gè)時(shí)間點(diǎn)觀察嗅鞘細(xì)胞在移植部位的存活狀況和對(duì)節(jié)細(xì)胞的保護(hù)作用，發(fā)現(xiàn)隨術(shù)后時(shí)間的延長，移植部位嗅鞘細(xì)胞的數(shù)量逐漸減少，14 d時(shí)已完全消失。移植的嗅鞘細(xì)胞在第7天能夠顯著增加存活節(jié)細(xì)胞的數(shù)量，且視網(wǎng)膜和視神經(jīng)殘段內(nèi)的腦源性神經(jīng)營養(yǎng)因子（brain-derived neurotrophic factor，BDNF）表達(dá)水平明顯上調(diào)，說明移植的嗅鞘細(xì)胞通過上調(diào)的BDNF發(fā)揮了神經(jīng)保護(hù)作用。為回答上調(diào)的BDNF究竟是來源于移植嗅鞘細(xì)胞，還是移植嗅鞘細(xì)胞刺激了宿主視網(wǎng)膜內(nèi)BDNF的分泌，王濤等[43]將培養(yǎng)的視網(wǎng)膜神經(jīng)節(jié)細(xì)胞劃傷后加入嗅鞘細(xì)胞條件培養(yǎng)液，發(fā)現(xiàn)嗅鞘細(xì)胞條件培養(yǎng)液增強(qiáng)損傷節(jié)細(xì)胞的活性，并促進(jìn)節(jié)細(xì)胞的數(shù)量和突起生長。經(jīng)檢測，條件培養(yǎng)液中BDNF表達(dá)明顯增強(qiáng)，用特異性中和性抗體阻斷條件培養(yǎng)液中的BDNF后，嗅鞘細(xì)胞條件培養(yǎng)液對(duì)損傷節(jié)細(xì)胞的保護(hù)作用完全消失，間接證明BDNF來源于移植的嗅鞘細(xì)胞。Huo等[44-45]還發(fā)現(xiàn)，植入1月齡視網(wǎng)膜色素變性大鼠視網(wǎng)膜下腔的嗅鞘細(xì)胞，能夠減輕Müller細(xì)胞損傷的反應(yīng)，保持恢復(fù)蛋白（recoverin）的表達(dá)，保護(hù)視網(wǎng)膜外色素層，增加外色素層中花生凝集素陽性的視錐細(xì)胞，減少caspase陽性的凋亡物質(zhì)，下調(diào)膠質(zhì)纖維酸性蛋白（glial fibrillary acidic protein，GFAP）并保持視網(wǎng)膜電圖的b波。

李英等[46]將成年大鼠單側(cè)視神經(jīng)在球后切斷，植入視神經(jīng)兩斷段之間的嗅鞘細(xì)胞在術(shù)后6個(gè)月遷移進(jìn)入視神經(jīng)遠(yuǎn)側(cè)段內(nèi)達(dá)10 mm，切斷的節(jié)細(xì)胞軸突與移植的嗅鞘細(xì)胞伴行長入視神經(jīng)遠(yuǎn)側(cè)段內(nèi)達(dá)10 mm，證明移植的嗅鞘細(xì)胞能促進(jìn)損傷視網(wǎng)膜神經(jīng)節(jié)細(xì)胞軸突的再生。植入視神經(jīng)的嗅鞘細(xì)胞不但能夠在視神經(jīng)夾傷后促進(jìn)節(jié)細(xì)胞軸突的再生，同時(shí)還有助于再生軸突的再髓鞘化[47]。移植嗅鞘細(xì)胞聯(lián)合應(yīng)用玻璃體腔內(nèi)注射重組人類GDNF在成年大鼠不完全性視神經(jīng)損傷后，對(duì)促進(jìn)視覺功能恢復(fù)更為有效[48]。

3.嗅鞘細(xì)胞對(duì)腦損傷修復(fù)的作用：有限的研究表明，嗅鞘細(xì)胞移植對(duì)腦損傷的修復(fù)同樣具有促進(jìn)作用。Smale等[49]切斷穹隆-海馬傘后立即于損傷區(qū)內(nèi)植入嗅鞘細(xì)胞，4周后發(fā)現(xiàn)嗅鞘細(xì)胞可在損傷區(qū)內(nèi)存活，并顯著抑制損傷區(qū)內(nèi)星形膠質(zhì)細(xì)胞反應(yīng)和損傷神經(jīng)纖維的再生。Teng等[50]切斷大鼠一側(cè)黑質(zhì)紋狀體多巴胺能神經(jīng)元軸突，植入損傷區(qū)的嗅鞘細(xì)胞促進(jìn)了多巴胺能軸突的再生，并完全抑制了損傷區(qū)內(nèi)膠質(zhì)瘢痕的形成。這些不同的研究表明，中樞神經(jīng)系統(tǒng)不同神經(jīng)元均可對(duì)移植的嗅鞘細(xì)胞產(chǎn)生良好的修復(fù)反應(yīng)。因此，嗅鞘細(xì)胞很有可能成為中樞神經(jīng)再生的通用促進(jìn)劑。

多種治療已被證明有促進(jìn)中樞神經(jīng)系統(tǒng)尤其是脊髓損傷修復(fù)的作用，但在單一因素的作用下，受損神經(jīng)纖維再生和截癱肢體運(yùn)動(dòng)功能的恢復(fù)程度均十分有限。中樞神經(jīng)損傷是成因多元化的復(fù)雜性疾病，如何在系統(tǒng)水平上理解和評(píng)價(jià)多組分、多靶點(diǎn)治療的作用機(jī)理和療效已成為日趨熱門的應(yīng)用系統(tǒng)生物學(xué)學(xué)科的前沿方向。近年來已出現(xiàn)采用雞尾酒式復(fù)合干預(yù)措施來修復(fù)機(jī)理錯(cuò)綜復(fù)雜的脊髓損傷的趨勢，國際神經(jīng)科學(xué)領(lǐng)域高影響因子雜志上已發(fā)表多項(xiàng)細(xì)胞移植加某種藥物聯(lián)合治療的研究成果，足以體現(xiàn)此類研究的必然趨勢。

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