閬庡幓鍗佸勾瑕嬭瓑浜嗗共绱拌優鍩虹鐢熺墿瀛稿拰鑷ㄥ簥杞夊寲鐮旂┒鐨勯閫熺櫦(f膩)灞�銆傚共绱拌優鍒嗛洟銆佸垎鍖栧拰绱斿寲锛屽共绱拌優鐗规€�銆� 鍔熻兘缍寔鍜岀┅(w臎n)瀹氭摯澧炴妧琛撴柟妗堜笉鏂峰畬鍠�锛岃嚚搴婅│椹楀ぇ閲忔秾鐝�(xi脿n)銆傛帰绱㈠共绱拌優鍦ㄦ暣褰慨寰╃編瀹归牁鍩熺殑绯荤当(t菕ng)鍖�銆佺 瀛稿寲銆佽(gu墨)鑼冨寲鍜屾婧栧寲锛屼互鍙婂畨鍏ㄦ湁鏁堟噳鐢ㄨ矾寰戠殑鍏辫瓨锛屽凡鍏峰倷鎵庡鐨勭瀛哥悊璜栧拰瀵﹁笎鍩虹銆傛湰鍏辫瓨閭€璜嬪湅鍏у骞茬窗鑳炲熀绀庣爺绌剁殑涓€绶氬皥瀹跺拰鏁村舰淇京缇庡澶栫闋樺煙骞茬窗鑳炵爺绌剁殑鍓嶆部鑷ㄥ簥鐮旂┒灏堝鍏卞悓鎾板锛岄仈鎴愮殑姣忛爡闄宠堪鍜屾帹钖﹀潎鑷冲皯鏈�3浣嶇浉闂滈牁鍩熺殑灏堝绺界祼銆傜敱浜庣洰鍓嶅共绱拌優闋樺煙鐮旂┒绱涚箒鑰屽京闆�锛屾湰鍏辫瓨涓嶅彲鑳借В姹烘墍鏈夌殑鐤戞儜锛屾棬鍦ㄦ簼閫氬拰鎻愰珮鎴戝湅鏁村舰淇京缇庡闋樺煙寰炰簨骞茬窗鑳炲熀绀庡拰鑷ㄥ簥鐮旂┒宸ヤ綔鑰呯殑瑾嶇煡锛屼互鏈熸洿濂藉湴鎺ㄥ嫊骞茬窗鑳炵殑鑷ㄥ簥杞夊寲鎳夌敤鐮旂┒銆傚笇鏈涙湰鍏辫瓨鐨勭櫦(f膩)琛�锛岃兘澶犳縺鐧�(f膩)瑭查牁鍩熸湭渚嗙殑楂樿唱閲忕爺绌跺幓閫愭鎺㈢储鍜岃В姹哄湪鏈叡璀樹腑鏈В姹虹殑鐩搁棞鍟忛銆�
1 绺藉墖
鏈叡璀樻墍鎸囧共绱拌優鏄竴椤炲悓鏅傚叿鍌欒嚜鎴戞洿鏂拌兘鍔涘拰鍒嗗寲娼涜兘鐨勭窗鑳�锛涘彲浠ヤ締鑷儦鑳庣祫绻旓紝涔熷彲浠ヤ締鑷垚楂旂祫绻�锛涜嚜楂旀垨鑰呯暟楂�锛岄珨澶栧垎闆�銆佺磾鍖栨績绺�銆佸煿椁�(y菐ng)銆佸偝浠ｆ垨鑰呮槸涓嶅煿椁�(y菐ng)銆佷笉鍌充唬锛屾柊楫垨鑰呭噸瀛�銆�
1.1闁嬪睍骞茬窗鑳炶嚚搴婂墠鐮旂┒鍜岃嚚搴婄爺绌剁殑瑕佹眰
2015 骞�锛屽湅瀹惰(w猫i)鐢熷拰瑷堝妰鐢熻偛濮斿摗鏈冿紙鐝�(xi脿n)鍦嬪琛�(w猫i)鐢熷仴搴峰鍝℃渻锛夊拰鍦嬪椋熷搧钘ュ搧鐩�(ji膩n)鐫ｇ鐞嗙附灞€锛堢従(xi脿n)鍦嬪 钘ュ搧鐩�(ji膩n)鐫ｇ鐞嗗眬锛夐€ｇ簩(x霉)鐧�(f膩)甯冦€婂共绱拌優鑷ㄥ簥鐮旂┒绠＄悊杈︽硶锛堣│琛岋級銆媅1]銆併€婂共绱拌優鍒跺姂璩噺鎺у埗鍙婅嚚搴婂墠鐮旂┒鎸囧皫 鍘熷墖锛堣│琛岋級銆媅2]鍜屻€婇棞浜庨枊灞曞共绱拌優鑷ㄥ簥鐮旂┒姗熸鍌欐宸ヤ綔鐨勯€氱煡銆媅3]涓夐爡鏀跨瓥锛屾蹇楄憲骞茬窗鑳炶綁鍖栬嚚搴婄爺绌� 鐨勭浉闂滄斂绛栬惤鍦般€傚共绱拌優鑷ㄥ簥鍓嶇爺绌跺拰鑷ㄥ簥鐮旂┒瑕佸湪閬靛惊閫欎笁闋呮斂绛栫殑鍘熷墖鎸囧皫涓嬮€茶銆�
1.1.1 骞茬窗鑳炶嚚搴婂墠鐮旂┒瑕佹眰
蹇呴爤鍤磋瑷▓鐮旂┒瑷堝妰銆佽閷勫牨鍛婂繀闋堢繑瀵﹀彲杩芥函銆佺⒑淇濊│椹楃鍚堢瀛稿拰閱�(y墨) 瀛哥殑瑕佹眰锛岀偤骞茬窗鑳炶嚚搴婅│椹楃爺绌舵彁渚涘繀闋堝叿鍌欑殑鍏呭垎绉戝渚濇摎(j霉)銆傛墍鐢ㄧ窗鑳炶姹傝垏鑷ㄥ簥绱拌優涓€鑷�銆傜窗鑳炵敘鍝� 鐨勭敓鐢㈠拰鍔犲伐蹇呴爤鍦ㄦ豢瓒宠棩鍝佺敓鐢㈣唱閲忕鐞嗚(gu墨)鑼冿紙good manufacture practices, GMP锛夌殑鐠�(hu谩n)澧冧笅閫茶锛涙澶栵紝閭� 闇€瑕佸皪绱拌優缇�锛岀窗鑳炲熀鍥犵祫绌�(w臎n)瀹氭€�銆佹垚 / 鑷� / 淇冪槫鎬�銆佺暟甯稿垎鍖栧強鐢熺墿瀛稿姛鑳藉拰鏁堟噳閫茶鍒嗘瀽閼掑畾銆傚嫊鐗╂ā鍨� 鐨勯伕鎿囬伒寰笡灏戯紙reduce锛夈€佸劒(y艒u)鍖栵紙refine锛夊拰浠ｆ浛锛坮eplace锛変笁鍊嬪師鍓�銆傛湁鏁堟€х爺绌惰ō瑷堝師鍓囪姹傦細妯℃摤鑷ㄥ簥瑭﹂ 姊濅欢锛岃冻澶犵殑绲�(t菕ng)瑷堝姛鏁�锛屽悎閬╄冻澶犵殑灏嶇収銆侀毃姗熸硶銆佺洸娉�锛屽缓绔嬪姂閲忔晥鎳夐棞绯荤瓑銆傚畨鍏ㄦ€х爺绌跺寘鎷細绱拌優鐢熺墿鍒� 甯冦€佺暟浣嶇暟甯稿垎甯冭垏鍒嗗寲鍙婂皪鍏朵粬闀风煭鏈熺殑鍙兘姣掑壇浣滅敤鐨勭洠(ji膩n)娓�銆�
1.1.2 骞茬窗鑳炶嚚搴婄爺绌剁殑瑕佹眰 骞茬窗鑳炶嚚搴婄爺绌舵妲嬮渶绗﹀悎鍦嬪瑕佹眰锛涘共绱拌優鑷ㄥ簥鐮旂┒闋呯洰鎳夌暥鍦ㄥ凡瀹屾垚 鍌欐鐨勬妲嬪鏂�锛涘共绱拌優鑷ㄥ簥鐮旂┒蹇呴爤鍏峰倷鍏呭垎鐨勭瀛镐緷鎿�(j霉)锛屾噳娆婅 鍙楄│鑰呭拰鍏溇鍋ュ悍闋愭湡鐨勫彈鐩婂強棰ㄩ毆锛� 闋愭湡鐨勫彈鐩婃噳瓒呴亷鍙兘鍑虹従(xi脿n)鐨勬悕瀹�銆傝嚚搴婄爺绌舵柟妗堟噳鐣剁鍚堟柊鐗堛€婅棩鐗╄嚚搴婅│椹楄唱閲忕鐞嗚(gu墨)鑼冦€媅4]鐨勮姹傦紝骞� 绱拌優鍒跺姂绗﹀悎銆婂共绱拌優鍒跺姂璩噺鎺у埗鍙婅嚚搴婂墠鐮旂┒鎸囧皫鍘熷墖锛堣│琛岋級銆媅2]鐨勮姹�锛屽悓鏅傞€氶亷姗熸鐨勫€悊瀵╂煡鍜� 瀛歌瀵╂煡骞舵彁浜ゅ湅瀹惰(w猫i) 鐢熷仴搴峰鍝℃渻鍜屽湅瀹惰棩鍝佺洠(ji膩n)鐫ｇ鐞嗗眬鍌欐銆傜爺绌剁祼鏉熷悗锛屾噳鐣跺皪鍙楄│鑰呴€茶闀锋湡闅ㄨí鐩�(ji膩n)娓�锛岃⿻鍍瑰共绱拌優鑷ㄥ簥鐮旂┒鐨勯暦鏈熷畨鍏ㄦ€у拰鏈夋晥鎬с€�
1.2 骞茬窗鑳炲強鍏剁浉闂滅敘鍝佸埗鍌欐妲嬬殑瑕佹眰
鈶村共绱拌優鍙婂叾鐩搁棞鐢㈠搧鍒跺倷姗熸锛堜互涓嬬啊绋辨妲嬶級寤鸿ō鎳夋湁绗﹀悎妯欐簴鐨� GMP 鐢熺敘杌婇枔锛氭暣楂旇惉绱�锛屽眬閮� 鐧剧礆锛涚鍚� YY0033 绗笁椤為啱(y墨)鐧傚櫒姊扮敓鐢㈡婧�锛涘竷灞€绗﹀悎钘ュ搧 GMP 瑕佹眰锛涙瘡鑷哄剙鍣ㄧ殑浣跨敤閮芥湁鐩告噳鐨勬婧栨搷 浣滄祦绋嬶紙standard operation procedure, SOP锛�銆�
鈶垫妲嬫噳寤虹珛绗﹀悎 GMP 瑕佹眰銆佸畬鏁寸殑骞茬窗鑳炲埗鍔戝埗鍌欒唱閲忕鐞� 楂旂郴锛屽苟瑷珛鐛ㄧ珛鐨勮唱閲忕鐞嗛儴闁€锛屽饱琛岃唱閲忎繚璀夊拰璩噺鎺у埗鐨勮伔璨�銆傛妲嬫噳鏍规摎(j霉)姣忕ó骞茬窗鑳炲埗鍔戠殑鐗规€у強 鍏跺埗鍌欏伐钘濋€茶棰ㄩ毆瑭曚及銆�
鈶舵妲嬫噳寤虹珛鍚堢悊鐨勮唱閲忕鐞嗙瓥鐣ワ紝鎸囧畾鍏烽珨鐨勫共绱拌優鍒跺姂鍒跺倷绠＄悊璨犺铂浜�銆佽唱 閲忕鐞嗚矤璨汉鍜岃唱閲忔巿娆婁汉銆傚悓鏅傚缓绔嬩汉鍝�銆佽ō鍌欑鐞嗘獢妗堬紝骞跺皪鐩搁棞浜哄摗瀹屾垚灏堟キ(y猫)鐭ヨ瓨銆佸畨鍏ㄩ槻璀�銆佹噳鎬ラ爯 妗堢殑鍩硅〒鍜岀辜绾�(x霉)鏁欒偛锛屽皪瑷倷閫茶瑷堝妰鎬ф牎椹楀拰缍锛岀⒑淇濆埗鍔戠敓鐢㈢殑婧栫⒑鎬с€�
2 鍦ㄦ暣褰慨寰╃編瀹归牁鍩熸噳鐢ㄧ爺绌跺父瑕嬬殑骞茬窗鑳為鍨�
2.1 楠ㄩ珦闁撳厖璩共绱拌優 楠ㄩ珦闁撳厖璩共绱拌優锛坆one marrow mesenchymal stem cells, BMMSCs锛夋槸寰為楂撶祫绻斾腑鍒嗛洟鐛插彇鐨勪竴椤為枔鍏� 璩共绱拌優锛孎(xi脿n)riedenstein 绛塠5]浜� 1976 骞撮娆″牨閬�銆侭MMSCs 鍙布澹佺敓闀�锛屽叿鏈夊悜涓儦灞ょ祫绻旂窗鑳炲垎鍖栫殑鑳藉姏銆傚咕 涔庢墍鏈夌殑閫犺绱拌優琛ㄩ潰妯欏織鐗╋紙CD34銆丆D14銆丆D45 绛夛級鍦� BMMSCs 涓憟闄版€ц〃閬擺6- 7]锛孊MMSCs 琛ㄩ潰琛ㄩ仈鐨勬 瑷樼墿鍖呮嫭鏁村悎绱狅紙CD49銆丆D29銆丩FA- 3锛�锛屽厤鐤悆铔嬬櫧瓒呭鏃忥紙CD54銆丆D102锛�锛岃绠＄窗鑳為粡闄勫垎瀛愶紙CD106銆� CD44銆丆D166锛夌瓑[8- 10]銆侭MMSCs 涓昏渚嗘簮浜庨楂撴恫锛屽彲閫氶亷楂傚墠涓婃绌垮埡鎶藉彇锛屼篃鍙嚜鑴涢銆佽偂楠�銆佽兏楠ㄧ瓑楠ㄤ腑 鐛插彇銆傛娊鍙栫殑楠ㄩ珦娑查€氶亷瀵嗗害姊害闆㈠績娉�銆佸叏楠ㄩ珦鍩归(y菐ng)璨煎绡╅伕娉曘€佹祦寮忕窗鑳炲剙鍒嗛伕娉曞拰鍏嶇柅纾佺彔娉曠瓑鍙閬� 鍑哄ぇ灏忓潎鍕�銆佺磾搴︾浉灏嶈純楂樼殑 BMMSCs[11]銆侭MMSCs 鐨勬摯澧為€熷害妤靛揩锛岀煭鏅傞枔鐨勫煿椁�(y菐ng)鍚庡嵆鍙嵅鍙栧ぇ閲忕殑绱拌優銆�
2.2 鑴傝偑渚嗘簮骞茬窗鑳� 1973 骞�锛孭oznanski 绛夊湪鑴傝偑涓櫦(f膩)鐝�(xi脿n)浜嗛浼间簬鎴愮簴缍ǎ鐨勭窗鑳烇紝鍦ㄩ珨澶栦篃鑳戒繚鎸佷唬璎濇椿鎬12]锛�2001 骞�锛� Zuk 绛夎瓑瀵﹂€欎簺绱拌優涓瓨鍦ㄩ枔鍏呰唱骞茬窗鑳炲苟鍛藉悕鐐鸿剛鑲締婧愬共绱拌優锛坅dipose- derived stem cells锛孉DSCs锛塠13]銆傚叾琛ㄩ仈鍩鸿唱绱拌優鐩搁棞妯欏織鐗╋紙CD29銆丆D44锛夈€侀枔鍏呰唱绱拌優妯欏織鐗╋紙CD73銆丆D90锛夛紝鍩烘湰涓嶈〃閬旈€犺婧愭€х窗鑳炴 蹇楃墿 CD45 鍙� MHC鈪＄浉闂滆泲鐧� HLA- DR[13- 14]銆傚緸鑴傝偑绲勭箶涓垎闆� ADSCs 鐨勪富瑕佹柟娉曟槸鑶犲師閰舵秷鍖栨硶锛屾搷浣� 绨″柈锛岀敘閲忚純楂橈紱姝ゅ閭勬湁绲勭箶濉婅布澹佹硶銆佸惛闄勬煴娉�銆佺洿鎺ラ洟蹇冩硶銆佹姊版尟钑╂硶绛�锛屼絾鏁堢巼杓冧綆[15- 17]銆傚湪鐢ㄨ啝鍘� 閰惰檿鐞嗚剛鑲祫绻斿悗锛屾敹闆嗙殑搴曞堡绱拌優鍦樿绋辩偤鑴傝偑琛€绠″熀璩墖娈碉紙stromal vascular fraction锛孲VF锛夛紝鏄竴椤炲寘鎷� ADSCs銆佽剛鑲墠楂旂窗鑳烇紙鑴傝偑绁栫窗鑳烇級銆佸懆绱拌優銆佸収鐨窗鑳炪€佸収鐨绱拌優銆佸柈鏍� / 宸ㄥ櫖绱拌優鍜岄€犺骞茬窗鑳炵瓑鍦ㄥ収 鐨勭暟璩€х窗鑳炵兢锛屼篃鍏锋湁淇冮€茬祫绻斿啀鐢熺殑鍔熻兘[18- 19]銆�
2.3 鑷嶅付闁撳厖璩共绱拌優 鑷嶅付闁撳厖璩共绱拌優锛坲mbilical cord mesenchymal stem cells, UCMSCs锛夋槸涓€绋嚜鑷嶅付鍒嗛洟鐨勯枔鍏呰唱骞茬窗鑳�锛� 鏈€鏃╁湪 21 涓栫磤鍒濊鍫遍亾[20]銆傝噸闈滆剤鍏х毊銆佽噸甯� Wharton's 鑶犺唱鍜岃绠″懆鍦嶇祫绻斾腑鍧囧彲鍒嗛洟鐛插緱 UCMSCs[21- 23]銆俇CMSCs 鍏锋湁鍏稿瀷鐨勯枔鍏呰唱骞茬窗鑳炶〃闈㈡蹇楃墿琛ㄩ仈鐗归粸锛孋D29銆丆D44銆丆D105銆丆D166銆丱CT- 4 鍜� c- myc 鍧囧憟 闄芥€ц〃閬�,CD34 鍜� CD14 鍧囧憟闄版€ц〃閬擺24]銆俇CMSCs 鍏锋湁闀锋湡鑷垜鏇存柊銆侀珮鎿村鎬у拰琛ㄥ瀷绌�(w臎n)瀹氭€25]銆傜洰鍓嶅皻鐒� 鍏獚鐨勫垎闆� UCMSCs 鏂规硶锛屼娇鐢ㄨ純澶氱殑鏂规硶鏈夌祫绻斿璨煎娉曞拰閰舵秷鍖栨硶銆俇CMSCs 鐨勪締婧愭槸閱�(y墨)鐧傚虎妫勭墿鑷� 甯�锛屽€悊涓婅純鏄撶嵅寰楃煡鎯呭悓鎰忔巿娆婂洖鏀跺埄鐢紝鍙楀埌鑷ㄥ簥杞夊寲鎳夌敤鐨勯潚鐫瀃26]銆�
2.4 姣涘泭闁撳厖璩共绱拌優 姣涘泭闁撳厖璩共绱拌優锛坔air follicle mesenchyma stem cell, HFMSCs锛夊垎甯冨湪鍏╁€嬮儴浣嶏細姣涘泭鐞冮儴鐨勭湡鐨钩 闋紙dermal papilla, DP锛夊拰姣涘泭鐞冮儴鏈€澶栧堡鐨勭湡鐨灅锛坉ermal papilla, DS锛夊収[1- 2]銆傞€氶亷鍛ㄦ湡鎬у湴鍦� DP 鍜� DS 闁撻伔 绉�锛屽鐝�(xi脿n)闅ㄦ瘺鐧�(f膩)鍛ㄦ湡鐨� DP 鍜� DS 鍔熻兘鎬ч噸绲刐3- 4]銆傜浉姣斾簬渚嗘簮浜庨楂�銆佽剛鑲€佽噸甯剁瓑绲勭箶鐨勯枔鍏呰唱骞茬窗鑳�锛� HFMSCs 鍏锋湁渚嗘簮璞愬瘜銆佸彇鏉愮啊鍠�銆佸皪姗熼珨鍓�(chu脿ng)鍌峰皬涓旂劇骞撮健闄愬埗绛夊劒(y艒u)榛�銆侶FMSCs 涔熷叿鏈夋垚楠ㄣ€佹垚鑴傚拰鎴愯粺楠� 娼涜兘锛岃〃闈㈤櫧鎬ф瑷樼墿鏈� CD44銆丆D73銆丆D90銆丆D105[5- 7]銆侶FMSCs 鐨勫垎闆㈡槸鐢ㄤ腑鎬ц泲鐧介叾 + 鑶犲師閰舵秷鍖栫毊鑴� 鑵轰笅 2 mm 浠ヤ笅鐨勬瘺鍥婁笅绔�锛屾摯澧炲煿椁�(y菐ng)鍚庨€氶亷琛ㄩ潰妯欏織鐗╁垎閬稿嚭 HFMSCs[8- 9]銆傜敱浜� HFMSCs 鍦ㄩ珨澶栧煿椁�(y菐ng)閬庣▼ 涓叾瑾樺皫鑳藉姏閫愭几鍠け锛屾墍浠ョ洰鍓嶉棞浜庣董鎸� HFMSCs 骞茬窗鑳炵壒鎬х殑鏂规硶涓昏鏄� 3D 鍩归(y菐ng)锛屽寘鎷嚫婊存硶銆丒CM 娉�銆丩BL 娉曠瓑[9- 12]銆�
2.5 鐗欓珦闁撳厖璩共绱拌優 鐗欓珦闁撳厖璩共绱拌優锛坔uman dental pulp stem cells, hDPSCs锛変綔鐐轰汉楂旂墮楂撶祫绻斾腑瀛樺湪鐨勪竴绋枔鍏呰唱骞茬窗鑳�锛岃垏鍏朵粬闁撳厖璩共绱拌優涓€妯ｅ叿鏈夊緢寮风殑澧炴畺鍔�銆佽嚜鎴戞洿鏂板拰澶氬悜鍒嗗寲鑳藉姏,鍚屾檪閭勫叿鏈夊厤鐤绡€(ji茅)鍔熻兘鍜屾經 鍦ㄧ殑绲勭箶鍐嶇敓鐗规€27- 28]銆俬DPSCs 鑸� BMMSCs 鍏锋湁鐩镐技鐨勫厤鐤〃鍨嬶紝鍚屾ǎ琛ㄩ仈 CD73銆丆D90 鍜� CD105锛屼笉琛ㄩ仈 CD14銆丆D34 鍜� CD45 绛夎〃闈㈡瑷�锛屼絾 hDPSCs 鍏锋湁鏇撮珮鐨勫娈栫巼鍜屽厠闅嗗舰鎴愯兘鍔沎27]銆傝縿浠婄偤姝�锛屽凡鍒嗛洟鍜岄憭 瀹氬嚭 8 绋笉鍚岀殑 hDPSCs锛屽叾涓噳鐢ㄦ渶鐐哄唬娉涚殑鏄� hDFSCs锛屽叾鍒嗛洟鍩归(y菐ng)鐨勬柟娉曡垏鍏朵粬绲勭箶闁撳厖璩共绱拌優鏂规硶 椤炰技[29]銆�
2.6 鑳氳儙骞茬窗鑳�銆佽獦灏庢€у鍔熻兘骞茬窗鑳炵瓑鍏朵粬骞茬窗鑳� 鑳氳儙骞茬窗鑳烇紙embryonic stem cells, ESCs锛夋槸涓€绋緸鏃╂湡鑳氳儙鎴栧収绱拌優鍦樹腑鍒嗛洟鍑轰締鐨勫叏鑳藉共绱拌優锛屽彲浠� 鍚� 3 鍊嬭儦灞ゅ垎鍖栵紝鍦ㄩ珨鍏ф垨楂斿鐠�(hu谩n)澧冨潎鍙瑾樺皫鍒嗗寲鐐烘楂斿咕涔庢墍鏈夌窗鑳為鍨媅30]銆侲SCs 琛ㄩ仈鐨勭壒鐣版€ф蹇� 鐗╁寘鎷� SSEA- 3銆丼SEA- 4銆乀RA- 1- 60銆乀RA- 1- 81銆乀RA- 2- 49/6E 鍜� Nanog[31]銆傜劧鑰岃儦鑳庡共绱拌優鐨勪娇鐢ㄤ粛瀛樺湪棰� 闅拰鍊悊鍟忛銆傝獦灏庢€у鍔熻兘骞茬窗鑳烇紙induced pluripotent stem cells锛宨PSCs锛夋槸鍒╃敤鍝轰钩鍕曠墿鐨勬垚楂旂窗鑳�锛岀敱浜� 宸ヨ綁鍏� Oct4銆丼ox2銆乧- Myc銆並lf4 鍥涚ó杞夐寗鍥犲瓙锛屼娇鎴愰珨绱拌優鍩�(zh铆)琛屽幓鍒嗗寲閫斿緫鑰屽舰鎴愰浼间簬鑳氳儙骞茬窗鑳炵殑澶氳兘 骞茬窗鑳瀃32]銆俰PSCs 鑸� ESCs 鎿佹湁鐩镐技鐨勫啀鐢熻兘鍔�锛岀悊璜栦笂鍙互鍒嗗寲鐐烘墍鏈夋垚楂斿櫒瀹�銆佺祫绻�锛屽叾琛ㄩ潰妯欏織鐗╄垏鏈垎 鍖栫殑 ESCs 椤炰技銆傜浉姣� ESCs锛宨PSCs 闈㈣嚚鐨勫€悊閬撳痉鐖杓冨皬锛屼絾 iPSCs 瑾樺皫鎶€琛撻潰鑷ㄨ憲瑾樺皫鏁堢巼浣�锛岀敤浜庢不 鐧傚瓨鍦ㄩ暦鏈熻叓鐦らⅷ闅瓑鎸戞埌(zh脿n)[33- 34]銆傚叾浠栫殑骞茬窗鑳為倓鍖呮嫭鑳庣洡銆佺緤姘翠互鍙婂翱娑茬瓑渚嗘簮闁撳厖璩共绱拌優锛岄€欎簺绱拌優 涔熷叿鏈夊鍚戝垎鍖栬兘鍔涘拰杓冮珮鐨勫娈栬兘鍔�銆�
3 骞茬窗鑳炰繚瀛樼殑瑕�(gu墨)鑼�
楂樿唱閲忕┅(w臎n)瀹氫繚瀛樺共绱拌優璩囨簮鏄共绱拌優鎳夌敤涓殑闂滈嵉鐠�(hu谩n)绡€(ji茅)锛屼綆婧喎鍑嶄繚瀛樻妧琛撶偤骞茬窗鑳炵殑閬嬭几銆侀暦鏈熷瓨 鍎层€佹椿鎬у拰鍔熻兘鐨勪繚瀛樻彁渚涗簡鑷抽棞閲嶈鐨勪繚璀�銆傜爺绌惰〃鏄庣祫绻斿拰绱拌優闆栫劧鍙互鍦� - 196 鈩冧綆婧笅闀锋湡淇濆瓨锛� 浣嗗嵒鏄撳湪闄嶆韩鍜屽京婧亷绋嬩腑鍙楁憾娑插噸绲愩€佽瀺鍖栦互鍙婃憾娑叉徊閫忓璁婂寲绛夊洜绱犵殑浣滅敤鑰岀櫦(f膩)鐢熸悕鍌穂35]銆傚喎鍑嶆悕鍌烽€� 甯稿師鍥犳槸鍦� - 60~0 鈩冪窗鑳炲収鍐版櫠褰㈡垚锛屽湪灏嶇窗鑳為€犳垚鐩存帴鎼嶅偡鐨勫悓鏅傚皫鑷寸窗鑳炲収澶栭吀鍫垮害銆佹徊閫忓绛夌櫦(f膩)鐢熸敼璁�銆傞€氶亷鍔犲叆鍐峰噸淇濊鍔戝拰绋嬪簭鎬ч檷婧紝鍙笡灏戠窗鑳炲収鍐版櫠褰㈡垚锛屾彁楂樼窗鑳炴椿鎬с€傚喎鍑嶄繚璀峰姂鏍规摎(j霉)鍏舵槸鍚︾┛ 閫忕窗鑳炶啘閫氬父鍒嗙偤鍏╁ぇ椤炲瀷锛屽嵆婊查€忔€у喎鍑嶄繚璀峰姂鍜岄潪婊查€忔€у喎鍑嶄繚璀峰姂[35]銆傛徊閫忔€у喎鍑嶄繚璀峰姂澶氱偤灏忓垎瀛� 涓€х墿璩�锛屽叾浣滅敤鐐哄急鍖栨按绲愭櫠閬庣▼锛屾笡灏戝皪绱拌優绲愭鍜屽姛鑳界殑鐮村锛屼富瑕佸寘鎷敇娌�銆佷簩鐢插熀浜炵牅锛圖MSO锛�銆� 涓欎簩閱囥€佷箼浜岄唶銆佷箼閰拌兒銆佺敳閱囩瓑銆傞潪婊查€忔€т繚璀峰姂澶氱偤澶у垎瀛愮墿璩�锛岄€氶亷闄嶄綆婧惰唱婵冨害渚嗘笡灏戜綆婧噸瀛樺皪绱� 鑳炵殑鎼嶅偡锛屼富瑕佸寘鎷捣钘荤硸銆佽仛涔欎簩閱�銆佺茎涔欏熀娣€绮�銆佽仛涔欑儻鍚″挴鐑烽叜銆佽憽鑱氱硸銆佺櫧铔嬬櫧绛�銆備笉鍚岀ó骞茬窗鑳炵殑浣� 婧敓鐗╃壒鎬т笉鐩稿悓, 鎳夊皪鍐峰噸鎼嶅偡鐨勮兘鍔涘悇鏈変笉鍚�銆傚洜姝�锛屾噳鐢ㄧ壒鏈夌殑鏈€浣充綆婧繚瀛樻柟娉曚繚瀛樹笉鍚岀殑骞茬窗 鑳炴墠鑳界⒑淇濆京婧悗鐨勫共绱拌優“瀹夊叏 - 鏈夋晥”[36- 38]銆�
4 鏁村舰淇京缇庡闋樺煙骞茬窗鑳炵殑涓昏鑷ㄥ簥鐮旂┒鏂瑰悜
4.1 鍦ㄥ鍔犵祫绻旇绠″寲鍜屾姉绾栫董鍖栦腑鐨勬噳鐢� 绲勭箶琛€閬嬮殰绀欐槸鏁村舰澶栫甯歌檿鐞嗙殑鍟忛锛屽共绱拌優鍙鐢ㄤ簬娌荤檪鐨摚缂鸿鍙婂叾浠栫祫绻旂己琛€鎬х柧鐥�銆傝嚚搴� 鍓嶇爺绌跺凡璀夊锛屽共绱拌優鏈変績閫茬窗鑳為伔绉汇€佹垚绠＄殑鑳藉姏锛屽彲鏀瑰杽鐨摚琛€娑插惊鐠�(hu谩n)锛屼績閫茬毊鐡ｆ垚娲籟39- 40]銆傚湪缂鸿鐨勬墜 閮ㄧЩ妞嶇毊鐡ｅ収鍙婂懆鍦嶇祫绻斾腑娉ㄥ皠 SVF锛屽彲瑙€瀵熷埌鐨摚琛€閬嬫湁鏄庨’鏀瑰杽锛屾墜鍔熻兘鏀瑰杽[41]銆傚共绱拌優鍦ㄤ笅鑲㈢己琛€鐤剧梾 涓篃鏈夋噳鐢�锛屽湪鍤撮噸涓嬭偄缂鸿鐨勭梾渚嬩腑锛岄€氶亷鑲岃倝鍏ф敞灏� CD133+ 鐨勫共绱拌優锛屽彲鍒烘縺鏂拌绠＄敓鎴怺42- 43]銆傚湪鐦㈢棔娌� 鐧傛柟闈�锛孊MMSCs 鍙敤浜庨爯闃茶偉鍘氭€х槩鐥曟偅鑰呯Щ妞嶅悗鐨啔绉绘鐗╃殑鏀剁府[13]銆傛澶�锛岀毊涓嬪眬閮ㄦ噳鐢� BMMSCs 鍙槑 椤敼鍠勪腑銆侀噸搴﹁悗绺€х棨鐦＄槩鐥�锛屼笖鐒℃槑椤壇浣滅敤[14]銆傞倓鏈夌爺绌舵噳鐢� ADSCs 娌荤檪绯荤当(t菕ng)鎬х‖鍖栫櫏鐨勬寚绔桨鐦�锛� 鐧�(f膩)鐝�(xi脿n)鍙績閫插壍(chu脿ng)闈㈡剤鍚�锛屾敼鍠勭柤鐥涚櫏鐙€鍜屾墜鍔熻兘[44]銆�
4.2 鍦ㄥ壍(chu脿ng)鍌峰悗鐨啔鍐嶇敓鑸囧壍(chu脿ng)闈㈡剤鍚堜腑鐨勬噳鐢� 鍓�(chu脿ng)鍌峰眳鐤剧梾璀滈浣�锛屽叾涓毊鑶氱己鎼嶆渶鐐哄鐧�(f膩)銆傚悓鏅傦紝绯栧翱鐥�銆佽剤绠＄柧鐥呯瓑寮曠櫦(f膩)鐨勭毊鑶氭桨鐦嶅壍(chu脿ng)闈篃鏄珮鐧�(f膩) 鐥匸45]銆傝繎骞翠締鐧�(f膩)鐝�(xi脿n)骞茬窗鑳炲彲閫氶亷鐩存帴鍒嗗寲銆佹梺鍒嗘硨鐢熼暦鍥犲瓙绛夊鍊嬮€斿緫鍙冭垏鐨啔鍐嶇敓銆傚湪澶栧偡灏庤嚧鐨勬€ユ€х毊 鑶氬叏灞ょ己鎼嶄腑锛屽眬閮ㄦ敞灏� ADSCs 鍙府鐭壍(chu脿ng)闈㈡剤鍚堟檪闁�锛屾笡灏戠辜鐧�(f膩)鎬х槩鐥曟敚绺�銆佽壊绱犳矇钁楀拰澧炵敓鐨勭櫦(f膩)鐢焄46]銆傚湪绯� 灏跨梾瓒�銆佹參鎬у壍(chu脿ng)闈㈢瓑澶氱ó闆ｆ剤鎬у壍(chu脿ng)闈㈢殑娌荤檪涓紝鍦ㄥ壍(chu脿ng)闈㈤倞绶ｅ強鍩哄簳娉ㄥ皠骞茬窗鑳炲彲鏈夋晥淇冮€茬祫绻旇绠℃柊鐢�銆佸姞閫� 鑲夎娊绲勭箶褰㈡垚銆佹敼鍠勭祫绻旇渚�锛屽悓鏅備績閫插壍(chu脿ng)绶ｈ璩舰鎴愮窗鑳炵殑澧炴畺锛屽姞閫熷壍(chu脿ng)闈㈠啀涓婄毊鍖栭€茶€屼績閫叉剤鍚圼47- 48]銆傜浉杓� 浜庣劇姣涘泭鐨勭毊鐗囷紝甯舵湁姣涚櫦(f膩)鐨勭毊鑶氱Щ妞嶇墿鍥犲惈鏈夋瘺鍥婂共绱拌優鍜屾洿澶氱殑琛ㄧ毊骞茬窗鑳�锛屽湪淇冮€叉參鎬ф桨鐦嶆剤鍚堜腑鍙� 閬斿埌鏇村ソ鐨勬晥鏋淸49]銆傜毊鑶氭摯寮典腑锛屽眬閮ㄧ殑寮靛姏鍙獦灏庤娑插惊鐠�(hu谩n)涓共绱拌優鍚戞摯寮电毊鑶氬眬閮ㄩ伔绉�锛屽湪灞€閮ㄥ畾妞嶅悗閫氶亷鍒嗗寲鍜屽悎鎴愮敓闀峰洜瀛愪績閫叉摯寮电毊鑶氱祫绻斿啀鐢焄50]銆傚彟鏈夌爺绌惰瓑瀵�锛屽共绱拌優鍦ㄤ績閫插厜鑰佸寲鍜岃“鑰佸悗鐨勭毊鑶氬啀 鐢熷勾杓曞寲绛夋柟闈㈡湁椤憲鏁堟灉[51]銆�
4.3 鍦ㄨ剛鑲Щ妞嶅悗鍐嶇敓涓殑鎳夌敤 鑴傝偑绉绘鏄粺绲勭箶钀庣府鍜岀己鎼嶄慨寰╃殑閲嶈鏂规硶锛屼絾绉绘鐨勮剛鑲祫绻旂敱浜庣己涔忚渚涜垏鐢熼暦鍥犲瓙锛屽父鍑虹従(xi脿n)杓� 楂樼殑鍚告敹鐜囧強绾栫董鍖�銆侀垼鍖栫瓑鐝�(xi脿n)璞★紝褰遍熆鍏剁檪鏁圼52]銆傛噳鐢ㄥ共绱拌優杓斿姪鑴傝偑绉绘锛坈ell- assisted lipotransfer, CAL锛� 鍚庤剛鑲窗鑳炴垚娲荤巼鎻愰珮锛岀祫绻旂祼妲嬪舰鎱�(t脿i)鏇村ソ锛屽苟鐧�(f膩)鐧ユ洿灏慬53- 55]銆傚湪涔虫埧鑴傝偑濉厖涓�锛屽姞鍏ュ共绱拌優鍙互鎻愰珮绉绘 鍚庤剛鑲殑鎴愭椿鐜�锛屾笡灏戣剛鑲敞灏勫悗绾栫董鍖栥€佸泭鑵瓑骞剁櫦(f膩)鐧ョ殑鐧�(f膩)鐢熺巼锛屽悓鏅傛湭瑙€瀵熷埌鑴傝偑鐣板父澧炴畺銆佽叓鐦ょ瓑骞剁櫦(f膩) 鐧ョ殑鐧�(f膩)鐢焄55- 56]銆傚彟澶栵紝鍦ㄥ崐闈㈣悗绺殑娌荤檪涓�锛屼篃瑙€瀵熷埌鎳夌敤 CAL 鍙彁楂樿剛鑲殑鎴愭椿鐜嘯57]銆�
4.4 鍦ㄦ瘺鐧�(f膩)鍐嶇敓涓殑鎳夌敤 鑴櫦(f膩)鏄洶鎿剧従(xi脿n)浠ｄ汉鐨勯噸瑕佸晱椤岋紝闄や簡鑸囬泟婵€绱犱唬璎濈墿浜屾矮鐫叜鐩搁棞鐨勪唬璎濋殰绀欐湁闂�锛屼篃鑸囨瘺鍥婂懆鍦嶈绠� 鍖栨笡灏戝拰鐢熼暦鍥犲瓙澶卞幓骞宠 鏈夐棞[58]銆傚共绱拌優鍒嗘硨鐨勮绠″収鐨敓闀峰洜瀛愩€佽倽绱拌優鐢熼暦鍥犲瓙銆佽儼宄剁礌妯ｇ敓闀峰洜瀛�銆� 琛€灏忔澘琛嶇敓鐢熼暦鍥犲瓙绛夊绋窗鑳炲洜瀛怺59]锛屼竴鏂归潰鍙鎺у京闆滅殑姣涚櫦(f膩)鐢熼暦鍛ㄦ湡锛屽彟涓€鏂归潰鍙績閫叉瘺鍥婂懆鍦嶇殑琛€ 绠″寲[60]锛岃獦灏庢瘺鍥婄湡鐨钩闋娈栧強瑾挎帶姣涘泭鐢变紤姝㈡湡閫插叆鐢熼暦鏈�锛屼績閫叉瘺鐧�(f膩)鐢熼暦銆佹姣涚櫦(f膩)鑲茬偤绲傛瘺[61- 62]銆傚湪鑴� 鐧�(f膩)鍗€(q奴)鍩熺毊鑶氬収娉ㄥ皠 ADSCs 鍜� SVF锛屽彲瑙€瀵熷埌娉ㄥ皠鍗€(q奴)鍩熸瘺鐧�(f膩)瀵嗗害鏈夋墍澧炲姞銆佹瘺鐧�(f膩)鐩村緫椤憲澧炵矖[63- 64]銆侫DSCs 鐨� 姊濅欢鍩归(y菐ng)鍩轰篃鍏锋湁淇冮€叉瘺鐧�(f膩)鍐嶇敓鐨勬晥鏋�锛屽娆℃敞灏勫悗鏁堟灉鑸囬潪閭ｉ泟鑳虹檪鏁堟帴杩慬65]銆傝嚜楂� BMMSCs 鍙婅嚜楂� HFMSCs 涔熻鍫遍亾鍦ㄦ不鐧傞洠娌绘€ф枒鐗囩媭鑴櫦(f膩)鍜岄泟婵€绱犳€ц劔鐧�(f膩)涓湁椤憲浣滅敤[66]銆�
4.5 鍦ㄩ鑸囪粺楠ㄥ啀鐢熶腑鐨勬噳鐢� 鐩墠閲濆皪鍥犲壍(chu脿ng)鍌�銆佽叓鐦�銆佸厛澶╃暩褰㈢瓑灏庤嚧鐨勯鍜岃粺楠ㄧ己鎼嶇殑淇京锛岃嚚搴婁笂涓昏閲囩敤鐨勬槸鑷珨绲勭箶绉绘銆佺暟 楂旂祫绻旂Щ妞嶅拰鏇夸唬鐗╂鍏ョ瓑鏂规硶锛屼絾鎳夌敤鑼冨湇鍜屾不鐧傛晥鏋滄湁涓€瀹氱殑灞€闄愭€67- 69]銆侭MMSCs 鍜� ADSCs 鏄湪楠ㄥ拰 杌熼缂烘悕鑷ㄥ簥鐮旂┒鎳夌敤涓渶甯歌鐨勫共绱拌優椤炲瀷锛屽悜楠�銆佽粺楠ㄧ殑灞€閮ㄧ己鎼嶆敞灏� BMMSCs 鎴� ADSCs 鍙績閫茬祫绻� 淇京鍐嶇敓[70- 72]銆傚皣骞茬窗鑳炶垏鐢熺墿鏀灦鏉愭枡寰╁悎锛屼笉鍍呭彲鎻愰珮骞茬窗鑳炲埄鐢ㄦ晥鐜�锛岃€屼笖鏀灦鏉愭枡鐨勫紩鍏ヤ篃鐐哄共绱� 鑳炲啀鐢熸彁渚涙洿鏈夊埄鐨勫井鐠�(hu谩n)澧�锛屼娇鍏跺叿鏈夋洿绌�(w臎n)瀹氱殑绲愭鍜屾洿鍎�(y艒u)鍖栫殑鍔熻兘[73]銆傞棞绡€(ji茅)鑵斿収娉ㄥ皠 ADSCs銆丅MMSCs 鎴� hDPSCs锛屽彲浠ラ€氶亷瑾跨瘈(ji茅)灞€閮ㄧ値鐧ャ€佷績閫茶粺楠ㄥ啀鐢熶慨寰╁緸鑰岀珐瑙ｇ柤鐥�銆佹帶鍒堕棞绡€(ji茅)鐐庣殑鐧�(f膩)灞昜74]銆傝嚚搴婄爺绌堕’绀洪噰鐢� 鑷珨骞茬窗鑳炴不鐧傞缂烘悕鏄畨鍏ㄦ湁鏁堢殑锛屽皻鐒＄爺绌堕’绀虹櫦(f膩)鐢熺値鐧ャ€佹劅鏌�銆佺祫绻旈亷搴︾敓闀锋垨鑵槫鐧�(f膩)鐢熺瓑[75]銆�
5 骞茬窗鑳炶鐢熺墿鐨勬噳鐢ㄧ爺绌�
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