股骨頸截骨：利用板鉤遮擋周圍軟組織，充分顯露股骨頸和股骨頭。對于攣縮較重的髖關(guān)節(jié)，可以對小轉(zhuǎn)子部位進行適當?shù)乃山?，以充分釋放髖關(guān)節(jié)的活動度，便于下一步操作。在術(shù)中將試模放置在股骨頸部位，確定股骨頸截骨的長度和角度，確保股骨側(cè)的截骨能夠和假體有較好的匹配度。確定好截骨長度和角度后，利用擺鋸截斷股骨頸，取出股骨頭。此時為了減少股骨髓腔的出血量，可利用骨蠟涂抹股骨髓腔以減少出血。

體位與手術(shù)切口入路：患者采用健側(cè)臥位，健肢輕微屈膝屈髖，在前側(cè)髂前上棘、后側(cè)髂后上棘部位使用固定軟墊支撐，以維持側(cè)臥位，避免術(shù)中肢體發(fā)生后傾或前傾。切口采用后外側(cè)入路，切口以大轉(zhuǎn)子為中心，上方指向髂后上棘，下方在大腿外側(cè)沿股骨干長軸向下延伸。

在前一篇科普文章中，我們揭示了髖關(guān)節(jié)疼痛的基本情況。在這一篇文章里，我們將更系統(tǒng)地總結(jié)髖關(guān)節(jié)疼痛的不同病因，以便為大家提供全面參考。了解髖關(guān)節(jié)疼痛的潛在原因?qū)τ诰_診斷和有效治療是至關(guān)重要的。專業(yè)的骨科醫(yī)生和康復(fù)治療師通常會依據(jù)疼痛的性質(zhì)、發(fā)生位置、伴隨的癥狀等多方面因素，進行全面的評估和診斷。在好大夫平臺上，我們致力于為您提供豐富而深入的關(guān)于髖關(guān)節(jié)疼痛的信息和資源。若您或您的親人正在面臨這一問題，請不要猶豫，及時與我們的醫(yī)療專家取得聯(lián)系，共同探尋適合您的解決方案。

干細胞治療股骨頭壞死：最新進展及未來研究發(fā)展趨勢作者：LeiZhao,AlanDavidKaye,AaronJKaye,AlaaAbd-Elsayed.作者單位:DepartmentofOrthopedics,ShandongProvincialHospitalAffiliatedwithShandongUniversity,Jinan,250021,China.譯者：陶可（北京大學(xué)人民醫(yī)院骨關(guān)節(jié)科）摘要綜述目的：股骨頭壞死（ONFH）是一種常見病、多發(fā)病。它是由不同病因?qū)е碌难汗?yīng)中斷引起的。股骨頭壞死（ONFH）導(dǎo)致股骨頭軟骨下骨變性、壞死，最終導(dǎo)致股骨頭塌陷。股骨頭壞死（ONFH）致殘率較高，嚴重影響患者生活質(zhì)量，且常累及中青年人群。最新發(fā)現(xiàn)：近年來，干細胞和再生醫(yī)學(xué)的技術(shù)和理解不斷發(fā)展。許多研究報告了干細胞移植治療股骨頭壞死（ONFH）的成功結(jié)果。因此，干細胞移植有望成為治療股骨頭壞死（ONFH）的新方法。因此，在本報告中，我們評估了利用干細胞治療股骨頭壞死（ONFH）的現(xiàn)有技術(shù)和結(jié)果。通過計算機在線檢索2006年1月至2017年6月期間的PubMed和Cochrane圖書館數(shù)據(jù)庫，使用英文關(guān)鍵詞“治療、干細胞、股骨頭壞死”檢索相關(guān)文章。選取與股骨頭壞死（ONFH）治療相關(guān)的文獻。我們的檢索共獲得161篇文章，但只有9篇文章符合我們的納入標準并被納入我們的報告中。本綜述表明，細胞技術(shù)在治療股骨頭壞死（ONFH）方面已顯示出良好的證據(jù)。然而，這項技術(shù)還需要進一步深入研究，以更好地探索和解決更理想的方法來克服與細胞來源相關(guān)的困難。圖示：干細胞技術(shù)被廣泛用于治療股骨頭壞死（ONFH）、骨缺損、神經(jīng)退行性病變等相關(guān)疾病手術(shù)治療如果股骨頭壞死(ONFH)進展迅速且非手術(shù)治療無效，則需要手術(shù)治療。外科手術(shù)主要包括兩大類：股骨頭本身重建和全髖關(guān)節(jié)置換術(shù)(THA)。保留股骨頭的手術(shù)技術(shù)包括：髓芯減壓、截骨術(shù)以及有或無血供的植骨[36]。髓芯減壓是治療早期股骨頭壞死(ONFH)的重要手術(shù)方法之一。主要是通過髓芯減壓突破硬化區(qū)，導(dǎo)致骨內(nèi)壓降低、血液供應(yīng)改善[37]。髓芯減壓更適合早期股骨頭壞死(ONFH)患者。一些臨床醫(yī)生發(fā)明了血管化和非血管化骨移植物，或設(shè)計了用其他材料（例如鉭棒）支撐的支架治療股骨頭壞死(ONFH)[38]。目前植骨治療股骨頭壞死(ONFH)的適應(yīng)癥有：（1）帶血管腓骨移植；(2)帶血管蒂髂骨移植術(shù)；(3)游離腓骨移植；(4)骨瓣移植；(5)病灶清除、打壓植骨手術(shù)；(6)病灶切除、記憶合金網(wǎng)植入；(7)病灶切除、打壓植骨、多孔鉭釘支撐手術(shù)。各種植骨都存在問題，因此多孔鉭棒得到了廣泛的應(yīng)用。與傳統(tǒng)的單一打壓植骨相比，多孔鉭棒支撐組合在I-II期股骨頭壞死(ONFH)中具有明顯優(yōu)勢。一項研究發(fā)現(xiàn)，股骨頭髓芯減壓聯(lián)合植骨、2mm打壓植骨加多孔鉭棒支撐等手術(shù)方法對股骨頭壞死(ONFH)患者，可延長股骨頭壽命，推遲全髖關(guān)節(jié)置換術(shù)(THA)時間[39]。截骨術(shù)的目的是去除股骨頭承重區(qū)的壞死區(qū)。截骨術(shù)包括股骨轉(zhuǎn)子旋轉(zhuǎn)的內(nèi)翻或外翻截骨術(shù)等，以不改變股骨髓腔為原則[40,41]。如果股骨頭塌陷嚴重（ARCO分期、IIIC和IV），并且關(guān)節(jié)功能嚴重喪失或中度疼痛，應(yīng)選擇全髖關(guān)節(jié)置換術(shù)(THA)。傳統(tǒng)治療結(jié)合干細胞治療股骨頭壞死(ONFH)干細胞MSCs來源于中胚層間充質(zhì)，廣泛分布于骨髓、骨膜、肌肉、滑膜、滑液、肝臟、外周組織、臍帶血、脂肪、胎盤、胎肺、胎腎、臍帶等組織中[42,43]。從這些組織中分離提取出具有多向分化能力的間充質(zhì)干細胞，細胞具有很強的自我更新和增殖能力[44]。它們在特定的誘導(dǎo)條件下可以分化為骨、軟骨、脂肪組織、肌肉、肌腱和血管內(nèi)皮細胞，甚至可以分化為神經(jīng)細胞[45]。相關(guān)研究表明干細胞MSC同種異體移植不會發(fā)生排斥反應(yīng)[46]。它已廣泛應(yīng)用于干細胞移植、基因治療、組織工程和其他研究工作。對于許多難治性疾病，細胞移植似乎是一種相對有效的療法。移植的自體細胞通常具有特定的功能，包括修復(fù)受損區(qū)域，避免使用傳統(tǒng)藥物對身體產(chǎn)生的毒性作用或副作用[47]。間充質(zhì)干細胞已廣泛應(yīng)用于骨缺損、軟骨缺損、組織損傷、骨關(guān)節(jié)炎、股骨頭壞死等修復(fù)。間充質(zhì)干細胞也已應(yīng)用于臨床實踐的其他領(lǐng)域[48]。干細胞治療股骨頭壞死(ONFH)是當前研究的熱點，研究表明干細胞在特定條件下可以分化為成骨細胞。成骨細胞在骨壞死修復(fù)過程中發(fā)揮著重要作用，研究表明，使用骨髓干細胞移植到壞死股骨頭中可以使股骨頭壞死(ONFH)的發(fā)生率降低至0%[49]。髓芯減壓聯(lián)合干細胞MSC移植髓芯減壓后的干細胞MSC移植可以為壞死股骨頭的修復(fù)和重建提供種子細胞[16]。Tabatabaee等的一項研究中[14]，在髓芯減壓的基礎(chǔ)上，對18例28髖的股骨頭壞死(ONFH)患者進行自體骨髓移植，所有患者平均隨訪2年。所有患者的西安大略大學(xué)和麥克馬斯特大學(xué)平均骨關(guān)節(jié)炎指數(shù)(WOMAC)和視覺模擬量表(VAS)評分均顯著改善。磁共振成像（MRI）顯示聯(lián)合治療組有顯著改善。研究人員認為，這項技術(shù)可用于改善股骨頭壞死區(qū)域的修復(fù)，至少在股骨頭壞死(ONFH)的早期階段是這樣。Rastogi等[13]也得出結(jié)論，髓芯減壓聯(lián)合自體骨髓干細胞植入是一種安全有效的方法。Sen等進行了一項臨床對照研究，表明在髓芯減壓后將自體骨髓單核細胞注入核心道可以為治療股骨頭壞死(ONFH)帶來更好的臨床結(jié)果和髖關(guān)節(jié)存活率[15]。Ma等[18]評價基于髓芯減壓的骨髓血沉棕黃層（BBC）植入治療股骨頭壞死的效果。作者得出結(jié)論，在治療的第二年，92%的股骨頭壞死(ONFH)患者的髖關(guān)節(jié)功能得到改善。更重要的是，治療組ARCO分期I/II期髖部無進展率為100%，對照組為66.7%[18]。Zhang等等[17]指出，髓芯減壓聯(lián)合自體骨髓間充質(zhì)干細胞移植可以減輕疼痛，延緩或避免股骨頭塌陷。MRI評估發(fā)現(xiàn)軟骨病變面積顯著縮小，軟骨質(zhì)量顯著改善。Gangji等[19]比較了核心減壓聯(lián)合含有間充質(zhì)干細胞（MSCs）或自體成骨細胞（OB）的骨髓濃縮物（BMC）治療股骨頭壞死(ONFH)的效果。他們發(fā)現(xiàn)，除了減輕股骨頭壞死(ONFH)的疼痛之外，自體成骨細胞（OB）植入在延緩骨循環(huán)協(xié)會(ARCO)III期進展方面比干細胞BMC治療更有效。然而，其他研究人員卻得出了不同的結(jié)論。Lim等[11]進行了一項對照試驗，比較了兩組治療股骨頭壞死的臨床效果和影像學(xué)結(jié)果：一組采用多次鉆孔減壓聯(lián)合干細胞移植，另一組采用干細胞移植聯(lián)合其他髓芯減壓方法：刮除術(shù)、植骨術(shù)等。結(jié)論是兩組之間沒有統(tǒng)計學(xué)上的顯著差異。從本研究來看，對于ARCOI-II期塌陷期的股骨頭壞死(ONFH)，髓核減壓聯(lián)合干細胞MSC移植獲得了良好的手術(shù)效果，但對于塌陷后的ARCOIII-IV期患者，這種手術(shù)方式效果不佳。生物力學(xué)支持和干細胞MSC動脈輸注股骨頭壞死(ONFH)發(fā)生后，盡管進行了髖關(guān)節(jié)挽救治療，改善股骨頭內(nèi)的血液供應(yīng)始終是該疾病的主要治療方法之一。自體干細胞移植和血管再生技術(shù)可以在治療中發(fā)揮重要作用。Kocher等[50]證實干細胞MSCs和內(nèi)皮祖細胞可以促進缺血血流恢復(fù)。Kinnaird等[51]發(fā)現(xiàn)，將骨源干細胞肌肉注射到大鼠缺血后肢后，骨源干細胞可以促進側(cè)支循環(huán)和肢體功能恢復(fù)。此外，與血管生成相關(guān)的細胞因子基因表達水平增加。Mao等[12]進行了一項對照試驗，其中55例89髖的股骨頭壞死(ONFH)患者接受鉭棒植入聯(lián)合間充質(zhì)干細胞靶向動脈內(nèi)灌注，所有患者均隨訪36個月。隨訪36個月時，聯(lián)合治療組中有3個髖關(guān)節(jié)（6.25%）被發(fā)現(xiàn)臨床失敗，需要進行全髖關(guān)節(jié)置換術(shù)THA；相比之下，對照組中有9個髖關(guān)節(jié)（21.95%）接受了全髖關(guān)節(jié)置換術(shù)THA。與對照組相比，聯(lián)合治療在36個月時顯著改善了Harris髖關(guān)節(jié)評分(HHS)。他們的結(jié)論是，干細胞MSC動脈輸注是治療早期股骨頭壞死(ONFH)的有效且安全的方法。與開放式股骨頭干細胞移植相比，干細胞MSC選擇性動脈輸注具有干細胞存活更好、分化更好、操作創(chuàng)傷小、不良反應(yīng)少、患者依從性好等優(yōu)點。手術(shù)可達到以下效果：（1）疏通病變股骨頭，改善靜脈回流，降低骨內(nèi)壓，恢復(fù)或改善股骨頭的血液供應(yīng)。(2)改善或增加股骨頭壞死區(qū)及髖關(guān)節(jié)周圍組織的血液循環(huán)，為壞死股骨頭提供良好的局部血液供應(yīng)。(3)干細胞MSCs可以保護局部血管內(nèi)皮，促進血管內(nèi)皮細胞的修復(fù)、再生和血管生成。隨著干細胞干預(yù)的進一步研究，這種方法似乎對未來的股骨頭壞死(ONFH)患者有積極作用。骨組織工程和間充質(zhì)干細胞組織工程是應(yīng)用細胞生物學(xué)，在體外培養(yǎng)功能相關(guān)的活細胞，復(fù)合移植體內(nèi)組織缺損并完成修復(fù)和重建。干細胞MSCs具有較強的分化潛能和增殖能力，細胞在來源、分離方式、分化組織類型等方面對于修復(fù)股骨頭壞死(ONFH)骨缺損具有獨特的優(yōu)勢。因此，它是骨組織工程種子細胞最理想的選擇。干細胞MSCs制成的復(fù)合支架可用于加強股骨頭壞死區(qū)域的修復(fù)，但也可以用作細胞、基因和生長因子的生物載體。此外，間充質(zhì)干細胞可以整合細胞和受體來調(diào)節(jié)細胞功能。Kang等[52]報道采用自體髂骨松質(zhì)骨移植聯(lián)合間充質(zhì)干細胞移植治療股骨頭壞死(ONFH)患者，隨訪32個月，臨床療效良好。Kawate等[53]采用β-磷酸三鈣作為載體承載自體骨髓干細胞BMSCs植入股骨頭壞死部位聯(lián)合血管化腓骨移植治療股骨頭壞死(ONFH)，長期隨訪發(fā)現(xiàn)大部分股骨頭壞死部位患者緩解至影像學(xué)觀察不同程度的局部高密度新骨形成。該疾病已得到控制，表明組織工程方法具有更好的治療股骨頭壞死(ONFH)的潛力。Yamasaki等[54]報道22例（30髖）股骨頭壞死(ONFH)患者接受單核細胞聯(lián)合磷酸鈣治療，8例（9髖）股骨頭壞死(ONFH)患者僅接受磷酸鈣治療。平均隨訪時間為29個月。治療組股骨頭壞死面積減少，僅3髖（3/30）出現(xiàn)股骨頭塌陷，而對照組6髖（6/8）出現(xiàn)嚴重股骨頭塌陷。Xiao等[55]在復(fù)合骨上用自體骨髓間充質(zhì)干細胞結(jié)合重組人骨形態(tài)發(fā)生蛋白2修復(fù)了兔股骨頭壞死(ONFH)缺損，他們發(fā)現(xiàn)這種方法可以防止塌陷并能形成新的骨組織。骨組織工程的興起為干細胞MSCs治療股骨頭壞死(ONFH)提供了有力支持。干細胞MSC移植聯(lián)合細胞因子隨著更多研究確定股骨頭壞死(ONFH)病因和發(fā)病機制，細胞因子已成為股骨頭壞死(ONFH)治療的焦點。目前已發(fā)現(xiàn)多種細胞因子可促進干細胞MSCs分化為骨細胞和軟骨細胞[56]。股骨頭壞死(ONFH)基礎(chǔ)實驗中使用的細胞因子包括骨形態(tài)發(fā)生蛋白（BMP）、血管內(nèi)皮生長因子（VEGF）、堿性成纖維細胞生長因子（BFGF）、腫瘤壞死因子（TNF）等。這些因子可以誘導(dǎo)干細胞MSC不可逆地分化為成骨細胞，有的可以誘導(dǎo)新生血管形成并參與股骨頭壞死(ONFH)的修復(fù)[57]。Reddi等[58]得出結(jié)論，骨形態(tài)發(fā)生蛋白（BMP）可以使間充質(zhì)細胞首先分化為軟骨細胞，然后分化為成骨細胞。成骨細胞可用于治療股骨頭壞死，這與它們在促進新骨形成、血運重建和促進關(guān)節(jié)軟骨生長方面的作用有關(guān)。堿性成纖維細胞生長因子（BFGF）具有較強的成骨和誘導(dǎo)血管生成作用，與骨形態(tài)發(fā)生蛋白（BMP）聯(lián)合應(yīng)用效果優(yōu)于單獨應(yīng)用骨形態(tài)發(fā)生蛋白（BMP）。Jin等[59]通過堿性成纖維細胞生長因子（BFGF）和骨形態(tài)發(fā)生蛋白（BMP）作用于兔股骨頭壞死(ONFH)，觀察到壞死區(qū)域新生骨小梁的形成，由此，作者得出結(jié)論，堿性成纖維細胞生長因子（BFGF）和骨形態(tài)發(fā)生蛋白（BMP）可以顯著促進骨細胞和成纖維細胞的生長和增殖。血管生成因子促進股骨頭壞死區(qū)域相對于正常區(qū)域的血運重建。血管生成因子可以維持壞死區(qū)域的血液供應(yīng)，可能作為治療股骨頭壞死(ONFH)的有效手段。血管內(nèi)皮生長因子（VEGF）具有很強的促進內(nèi)皮生長和血管生成的作用，其他血管生成因子通過增強血管內(nèi)皮生長因子（VEGF）的表達和產(chǎn)生來全部或部分促進血管生成[60]。盡管許多研究證明生長和分化因子在骨壞死的治療中發(fā)揮著重要作用，但這些研究都是在體外或動物實驗中進行的，并沒有直接證據(jù)證明它們在人體中的有效用途。在這方面，較新的治療方法通?；趯Σ±磉^程的更好理解。隨著對股骨頭壞死(ONFH)過程了解的加深，各種生長和分化因子的作用將逐漸變得清晰，這種類型的治療可能會在未來出現(xiàn)[61]。?SurgicalTreatmentSurgicaltreatmentisindicatedifONFHprogressesrapidlyandnon-surgicaltreatmentisnoteffective.Thesurgicalproceduresincludetwomaincategories:thereconstructionofthefemoralheaditselfandTHA.Theoperationtopreservethefemoralheadincludescoredecompression,osteotomy,andbonegraftingwithorwithoutbloodsupply[36].CoredecompressionisoneoftheimportantsurgicalmethodsforthetreatmentofearlyONFH.Itismainlythroughcoredecompressiontobreakthroughthehardeningzone,leadingtoareductioninintraosseouspressureandimprovementofbloodsupply[37].Coredecompressionismoresuitableforearly-stagepatientswithONFH.Someclinicianshaveinventedvascularizedandnon-vascularizedbonegrafts,ordesignedasupportwithothermaterials,suchastantalumrods[38].Atpresent,theindicationsforbonegraftingare(1)vascularizedfibulargrafting;(2)withvascularpediclediliacbonegraft;(3)freefibulagrafting;(4)withboneflaptransplantation;(5)lesionremoval,compressionofbonegraftsurgery;(6)lesionremoval,memoryalloymeshimplantation;and(7)lesionremoval,impactionbonegraft,andporoustantalumnailsupportsurgery.Allkindsofbonegraftinghaveissues,andthus,poroustantalumrodiswidelyused.Comparedwithtraditionalsinglecompressionosteogenesis,thecombinationofporoustantalumrodsupporthasobviousadvantagesinstageI–IIONFH.Astudyfoundthatthecoredecompressionandboneimplant,2mmimpactionbonegraftingplusporoustantalumrodsupportingmethodsofoperationinONFHpatients,canprolongthelifeofthefemoralheadandpostponeTHAtime[39].Thepurposeofosteotomyistoremovethenecroticzonefromtheweight-bearingareaofthefemoralhead.Osteotomyincludesvarusorvalgusosteotomybythefemoralrotorrotationosteotomy,andsoon,withtheprincipleofnotchangingthemedullarycavityofthefemur[40,41].Ifthefemoralheadcollapseisserious(ARCO,IIICandIV),andthereisaseverelossofjointfunctionormoremoderatepain,THAshouldbechosen.?TraditionalTreatmentCombinedwithStemCellTherapyforONFHMSCsarederivedfrommesodermalmesenchymeandarewidelydistributedinthebonemarrow,bonemembrane,muscle,synovium,synovialfluid,liver,peripheraltissue,umbilicalcordblood,fat,placenta,fetallung,fetalkidney,umbilicalcord,andothertissues[42,43].MSCswithmulti-directionaldifferentiationabilityhavebeenisolatedandextractedfromthesetissues,andthecellshavestrongself-renewalandproliferationability[44].Theycandifferentiateintobone,cartilage,adiposetissue,muscle,tendon,andvascularendothelialcellsunderspecificconditionsofinductionandcanevendifferentiateintonervecells[45].RelatedstudieshaverevealedthatMSCallogeneictransplantationdoesnotundergorejection[46].Ithasbeenwidelyusedinstemcelltransplantation,genetherapy,tissueengineering,andotherresearchendeavors.Formanyrefractorydiseases,celltransplantationappearstobearelativelyeffectivetherapy.Transplantedautologouscellsusuallyhavespecificfunctions,includingrepairingdamagedregions,avoidingtoxiceffectsonthebodyorsideeffectscausedbytheuseoftraditionaldrugs[47].MSCshavebeenwidelyusedintherepairofbonedefects,cartilagedefects,tissueinjuries,osteoarthritis,andosteonecrosisofthefemoralhead.MSCshavealsobeenappliedinotherfieldsofclinicalpractice[48].StemcellsinthetreatmentofONFHarethefocusofcurrentresearch,whichhasdemonstratedthatstemcellscandifferentiateintoosteoblastsunderspecificconditions.Osteoblastsplayanimportantroleintheprocessofrepairingbonenecrosis,andstudieshaveshownthatusingbonemarrowstemcellstransplantationintoanecroticfemoralheadleadstoadecreaseintheincidencerateofONFHto0%[49].?CoreDecompressionCombinedwithMSCTransplantationMSCtransplantationaftercoredecompressioncanprovideseedcellsfortherepairandreconstructionofanecroticfemoralhead[16].InastudybyTabatabaeeetal.[14],basedoncoredecompression,autologousbonemarrowtransplantationwasperformedonONFHin18patientswith28hips,andallpatientswerefollowedupforanaverageof2years.ThemeanWesternOntarioandMcMasterUniversitiesOsteoarthritisIndex(WOMAC)andvisualanalogscale(VAS)scoresinallpatientsimprovedsignificantly.Magneticresonanceimaging(MRI)showedasignificantimprovementinthecombinationtreatmentgroup.Theresearchersbelievethatthistechniquecanbeusedtoimprovetherepairoffemoralheadnecroticarea,atleastintheearlystagesofONFH.Rastogietal.[13]alsoconcludedthatcoredecompressioncombinedwithautologousbonemarrowstemcellimplantationisasafeandeffectivemethod.Senetal.conductedaclinicalcontrolledstudy,whichshowedautologousbonemarrowmononuclearcellinstillationintothecoretractaftercoredecompressioncanresultinbetterclinicaloutcomesandhipsurvivalfortreatingONFH[15].Maetal.[18]evaluatedtheeffectofbonemarrowbuffycoat(BBC)implantationbasedoncoredecompressionfortreatmentofosteonecrosisofthefemoralhead.Authorsconcludedthatduringthesecondyearoftreatment,improvementinhipfunctionwasnoticedin92%ofpatientswithONFH.Moreimportantly,thenon-progressionrateforstageI/IIhipswas100%inthetreatmentgroupand66.7%inthecontrolgroup[18].Changetal.[17]indicatedthatthecoredecompressioncombinedwithautologousbonemarrowMSCstransplantationcanreducepainanddelayoravoidfemoralheadcollapse.AssessmentbyMRIfoundthatthecartilagelesionareawassignificantlyreducedandthecartilagequalitywasimprovedsignificantly.Gangjietal.[19]comparedcoredecompressioncombinedwithbonemarrowconcentrate(BMC)containingmesenchymalstemcells(MSCs)orautologousosteoblasticcells(OB)totreatONFH.TheyfoundthatOBcellimplantationwasmoreefficaciousthanBMCtreatmentindelayingtheprogressiontoAssociationResearchCirculationOsseous(ARCO)stageIIIinadditiontoreducingpaininONFH.However,otherresearchershavehaddifferentconclusions.Limetal.[11]conductedacontrolledtrialinwhichtheclinicaleffectsandradiologicalresultsoftwogroupsoftreatmentforosteonecrosisofthefemoralheadwerecompared:Onegrouputilizedtheuseofmultipledrillingcoredecompressioncombinedwithstemcelltransplantation,andtheothergrouputilizedtheapplicationofothercoredecompressionmethod,curettage,andbonegrafting.Theconclusionwasthattherewasnostatisticallysignificantdifferencebetweenthetwogroups.Fromthisstudy,forthecollapseoftheARCOstageI–IIperiodofONFH,coredecompressionandMSCtransplantationobtainedagoodsurgicaloutcome,butforpost-collapseoftheARCOstageIII–IVpatients,thissurgicalapproachwasineffective.?BiomechanicalSupportandMSCsArterialInfusionAfterONFHanddespitehipsalvagetreatment,improvingbloodsupplywithinthefemoralheadisalwaysoneofthemaintreatmentsofthedisease.Autologousstemcelltransplantationandvascularregenerationtechnologiescanplayanimportantroleinmanagement.Kocheretal.[50]confirmedthatMSCsandendothelialprogenitorcellscanpromoteischemicbloodflowrecovery.Kinnairdetal.[51]foundthatafterintramuscularinjectionofbone-derivedstemcellsintotheischemichindlimbsofrat,bone-derivedstemcellscouldpromotecollateralcirculationandlimbfunctionrecovery.Inaddition,thelevelofcytokinegeneexpressionassociatedwithangiogenesiswasincreased.Maoetal.[12]conductedacontrolledtrialinwhich55patientswith89hipsofONFHunderwenttantalumrodimplantationincombinationwithtargetedintra-arterialinfusionofMSCs,andallpatientswerefollowedupfor36months.At36monthsoffollow-up,threehipsinthecombinedtreatmentgroup(6.25%)werefoundtobeclinicallyfailedandrequiredTHA;incontrast,ninehips(21.95%)receivedTHAinthecontrolgroup.Comparedtothecontrolgroup,combinationtreatmentsignificantlyimprovedtheHarrishipscore(HHS)at36months.TheyconcludedthatMSCarterialinfusionisaneffectiveandsafemethodforearlyONFH.Comparedwithopenfemoralheadstemcelltransplantation,MSCselectivearterialinfusionhastheadvantagesofbetterstemcellsurvival,betterdifferentiation,lessinvasiveoperation,lessadversereaction,andgoodpatientcompliance.Theoperationmayachievethefollowingeffects:(1)Dredgethediseasedfemoralhead,improvethevenousreturn,decreasetheintraosseouspressure,andrestoreorimprovethebloodsupplyofthefemoralhead.(2)Improveorincreasethebloodcirculationofthetissuesaroundthefemoralheadnecroticregionandthehip,providingagoodlocalbloodsupplyforthenecroticfemoralhead.(3)MSCscanprotectthelocalvascularendotheliumandpromotetherepair,regeneration,andangiogenesisofvascularendothelialcells.Withadditionalresearchusingstemcellintervention,itappearsthismethodwillbepositiveforfutureONFHpatients.?BoneTissueEngineeringandMSCsTissueengineeringistheapplicationofcellbiology,functionallyrelatedlivingcells,whichculturedinvitro,compositetransplantationinvivotissuedefectandcompleterestorationandreconstruction.MSCshavestrongdifferentiationpotentialandproliferationability,andthecellshaveuniqueadvantagesforrepairingONFHbonedefectsintermsofsource,separationmode,anddifferentiatedtissuetype.Thus,itisthemostidealchoiceforbonetissueengineeringseedcells.ThecompositescaffoldsmadeofMSCscanbeusedtoreinforcetherepairofnecroticdefectsinthestructurebutcanalsobeusedasabiologicalcarrierforcells,genes,andgrowthfactors.Inaddition,MSCscanintegratecellsandreceptorstoregulatecellularfunction.Kangetal.[52]reportedusingautoiliaccancellousbonegraftcombinedwithMSCtransplantationforONFHpatientswithfollow-upfor32monthsdemonstratinggoodclinicalefficacy.Kawateetal.[53]usedbeta-tricalciumphosphateasthecarrierloadbearingautologousBMSCsimplantedintotheareaoftheheadnecrosiscombinedwithvascularizedfibulargraftingfortreatmentofONFH,andlong-termfollow-upfoundthatmostpatientswithosteonecroticsiteswererelievedtovaryingdegrees,imagingobservedlocalhighdensityofnewboneformation.ThediseasewasundercontrolandindicatedthatthetissueengineeringapproachhadabetterpotentialforthetreatmentofONFH.Yamasakietal.[54]reportedthat22cases(30hips)ofONFHpatientsweretreatedwithmononuclearcellscombinedwithcalciumphosphateandeightcases(ninehips)ofONFHpatientsweretreatedwithcalciumphosphateonly.Theaveragefollow-upwas29months.Inthetreatmentgroup,thefemoralheadnecroticareawasreduced,andonlythreehips(3/30)developedfemoralheadcollapse,whilesixhips(6/8)inthecontrolgroupdevelopedseriousfemoralheadcollapse.Xiaoetal.[55]repairedrabbitONFHdefectswithautologousbonemarrowMSCsoncompositebonecombinedwithrecombinanthumanbonemorphogeneticprotein2.Theyfoundthatthismethodpreventedthecollapseandcanformnewbonetissue.TheriseofbonetissueengineeringprovidesastrongsupportforthetreatmentofONFHbyMSCs.?MSCTransplantationCombinedCytokineWithadditionalresearchidentifyingONFHetiologyandpathogenesis,cytokineshavebecomeafocusofONFHtherapy.Atpresent,manycytokineshavebeenfoundtopromotethedifferentiationofMSCsintobonecellsandchondrocytes[56].ThecytokinesusedinbasicexperimentsinONFHincludebonemorphogeneticproteins(BMP),vascularendothelialgrowthfactor(VEGF),basicfibroblastgrowthfactor(BFGF),tumornecrosisfactor(TNF),andothers.ThesefactorscaninduceMSCsirreversiblytodifferentiateintoosteoblasts,andsomecaninduceneovascularizationandparticipateinrepairofONFH[57].Reddietal.[58]concludedthatBMPcancausemesenchymalcellstofirstdifferentiateintochondrocytesandthendifferentiateintoosteoblasts.Osteoblastsmaybeusedinthetreatmentoffemoralheadnecrosisrelatedtotheirroleinpromotingnewboneformation,revascularization,andpromotingarticularcartilagegrowth.BFGFhasastrongroleinosteogenesisandinducedangiogenesis,combinedwithBMPeffectisbetterthantheapplicationofBMPalone.Jinetal.[59]throughtheBFGFandBMProleinrabbitONFH,observedinnecroticregionsnewbonetrabeculaeandthus,authorsconcludedthatBFGFcombinedwithBMPcansignificantlypromotegrowthandproliferationofbonecellsandfibroblasts.Angiogenicfactorspromoterevascularizationoffemoralheadnecroticarearelativetothenormalregions.AngiogenicfactorscanmaintainbloodsupplytonecroticregionsandmaybeusedasaneffectivemeansoftreatmentforONFH.VEGFhasastrongroleinpromotingendothelialgrowthandangiogenesis,andotherangiogenicfactorspromotingangiogenesisinwholeorinpartbyenhancingtheexpressionandproductionofVEGF[60].Althoughmanystudieshavedemonstratedthatgrowthanddifferentiationfactorsplayasignificantroleinthetreatmentofbonenecrosis,thesestudieswereinvitroorinanimalexperiments,andthereisnodirectevidencetoprovetheireffectiveuseinhumans.Inthisregard,newermethodsoftreatmentaretypicallybasedonimprovedunderstandingofpathologyprocesses.WithimprovedunderstandingoftheONFHprocess,theeffectsofvariousgrowthanddifferentiationfactorswillgraduallybecomeclearerandthistypeoftreatmentmaybeseeninthefuture[61].StemCellTherapyforOsteonecrosisoftheFemoralHead:CurrentTrendsandComprehensiveReviewAbstractPurposeofreview:Osteonecrosisofthefemoralhead(ONFH)isacommonandfrequentlyoccurringdisease.Itiscausedbyinterruptionofbloodsupplywithdifferentetiologies.ONFHleadstodegenerationandnecrosisofthesubchondralboneofthefemoralheadandeventuallycollapseofthefemoralhead.ONFHhasahighdisabilityrate,seriouslyaffectingthequalityoflivingofpatients,andofteninvolvesmiddle-agedandyoungerpeople.Recentfindings:Inrecentyears,thetechnologyandunderstandingofstemcellsandregenerativemedicinehavebeendevelopingrapidly.NumerousstudieshavereportedsuccessfulresultsinthetreatmentofONFHbystemcelltransplantation.Thus,stemcelltransplantationisexpectedtoserveasanewmethodinthetreatmentofONFH.Inthepresentreport,therefore,weevaluatedcurrenttechniquesandoutcomesutilizingstemcellsinthetreatmentofONFH.Acomputer-basedonlinesearchofPubMedandCochraneLibrarydatabasesbetweenJanuary2006andJune2017wasperformedtosearchrelatedarticlesusingthekeywordsof"treatment,stemcell,osteonecrosisofthefemoralhead"inEnglishlanguage.LiteraturerelatedtothetreatmentofONFHwasselected.Oursearchobtainedatotalof161articles,butonly9articlesmetourinclusioncriteriaandwereincludedinourreport.ThepresentreviewrevealsthatcelltechnologyhasdemonstratedgoodevidenceinthetreatmentofONFH.However,thistechnologyneedsadditionalin-depthstudytobetterexploreandappreciatemoreidealwaystoovercomedifficultiesassociatedwithsourceofcells.文獻出處：LeiZhao,AlanDavidKaye,AaronJKaye,AlaaAbd-Elsayed.StemCellTherapyforOsteonecrosisoftheFemoralHead:CurrentTrendsandComprehensiveReview.Review,CurrPainHeadacheRep.2018May3;22(6):41.doi:10.1007/s11916-018-0700-x.