2017 3 37 3 Basic& ClinicalMedicine March2017 Vol.37 No.3 间充质干细胞是一类具有自我更新能力和多向分化潜能的成体干细胞, 应用于多种重大疾病及疑难杂症的治疗, 是目前临床转化前景最为广阔的干细胞类型 截止到 2016 年 12 月, 在美国临床试验网站 htps://clinicaltrials.gov/ 注册的间充质干细胞临床研究达到 677 项, 涉及到 8 大类 20 多种疾病 2015 年 8 月国家卫生和计划生育委员会 国家食品药品监管总局联合发布了 干细胞临床研究管理办法 ( 试行 ) 文件, 开启了我国首个干细胞临床研究管理的规范性指导文件, 将极大地推进干细胞临床研究和应用的进程 中国医学科学院在间充质干细胞基础及临床转化方面在国际上率先开展了间充质干细胞治疗多种疾病, 包括移植物抗宿主病 心血管疾病和自身免疫性肝病等临床实践 为了促进我国干细胞转化的蓬勃发展, 基于 10 余年多中心国家药理研究基地干细胞安全性和有效性临床研究的经验积累, 归纳总结了中国医学科学院干细胞治疗多种疾病的临床方案, 作为系列报道 櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒 :1001 6325(2017)03 0291 05 干细胞专题 1, 1, 1, 1, 1, 1, 2,!"# 2 (1 5 6 789:6 ; 5 6 ; <=,78 100037; 2 5 6 789:6 2>?@AB5 +,-$% 78 <=,78 100005) C DE2!"#$ :R542 2 + 2 %&' :A (acutemyocardialinfarction, AMI) FG HI JKLMNO AMI, = #,- P,QRSTU,V = W:X#,YN L Z[\] FG^_01` U,ab c FG ]01(PCI) 01 ;,, L ^, +,-./013 D O +,- ' E O, -, \ :; ^, O [1] 01 O+,- O+,-,,- (BM MNCs) ()*+,-(MSCs),- (EPCs) ;+,-(CD34 +,-): ;,-(PBMNCs) <, +,-./01 AMIO 1, +,-./ AMI = ; (LVEF) 3%, [2 3] 3,,-O./1?./34(./` : )? +,-./? O 2: <,[ '+,-01 \]ab O # [4], +,-./1!"#$%O &' :, 3 :2016 12 16 :2016 12 23 :!"(2016YFA0101003); #$%&' # (2014ZX09101042 001,2014ZX09101042 002) (correspondingauthor):yangyjfw@126.com;zhaochunhua@vip.163.com
292 Basic&ClinicalMedicine 2017 37(3) +,- './34./` : () *./+,O-.E: E,/01 O Z./+,-O* O E ( ), C +,-234 564 E4 71O./8+9O E( :; ) +,-01 AMIO : <2,<<=%> E 8+9( :; )? +,-( @)56 AB./1 O&$ CD, > E;? +, -01 AMI1 O &', &$ ()*+,-./01 O FG HI?J 5 <, KZLMNO ()*+,-?? ST O HP : O2, ZQR O \ M<<SETUVWX E 8+9 ( :; )? +,-./1 OY #25+,-./01 AMIO-.E23 4, " +,-./01 AMI O 2: Z, O](-.:[\-../`./3]() AB./8+93] 1 NO^- HP NO^ - C2O _ 3 1 & \` MSC./01O a b-.: 1)c 30~75, ; 2) ST (STE MI); 3) STEMI2~5d, c _ 71 FG; 4) = F b F; 5) = b(lvef 45%); 6) Zb `( +,-01C _ ; 7)[.O+,-./0 1O 2 ()& a b -.O ] MSC. /01 AMIO 2: 1) ST O AMI; 2) O AMI; 3)AMI (Kilip4 ); 4) F ] 01 ; ; 5) Pa( = F = F = F I = M 2 /] ); 6)AMI = #= ` ; 7) ( :=( ); 8)AMI`[`+,-01; 9) K ( ); 10) ; 11) AIDS; 12);, ; ; ; ; 13), \4 <30mL/min, ; >133μmol/L; 14) a,gpt(alt)>3 a ; 15) ; O; 16) ; 17) ; 18) _O; 19) W 'O* ; 20). [ O ; 21) PCI : E : W # ;, ; F! ; 01 1; 22) < " OTUVWX; 23) #$ % /]> &J "O`( ' MRI _ : c; 24) O 3 *+,-./01./`( +,-234 564 0 1 O 1,Z AMI b,
(\ 293 ) *,-* @ 1(stromalcel derivedfac tor 1,SDF 1) U OE+E @,,- C O+,-./\` 0 SDF 1 +E @ 4(CXCchemokinereceptor4, CXCR4) \./+,-1 0?@ 1../,!?@ 0`?@ SDF 1O, SDF 1O 2 1 X3,+E CXCR4O+,-45 SDF 1 O 6 R 0?@ L, AMI?@5 SDF 1 `( F78E [5] O 9,SDF 1Z 1~ 3d R :,/Z 4~7d; b a [6 9] 8Eb, = <./ 4, 2( = AMI 1d\`./ [7,10] L,AMI 1d 8+97!, ; E < = >?@O,-:,- AB# @: C @,## =. /,-O564,Z+,-./O015, () @, `?@5 SDF 1O D `\`./, 0 E,-1 % O 1../:56,,-./O01 L./ @O ) :, E MSCsO./;/ `./8+9, E MSCsO56;L 1~2 =,./ @O #F G,H5Z IJ? ', KL?#MWX %> N O E,\`=# O,, TUVWX [11] VWX [12] PQ VWX [13] (./ 3d./ 4d) R' O = E <,AS O./ 8+9, \ MSCs56, MSCs01 O1, T]U = Y ' AMPK/ enos JAK/STAT ROCK/Erk _V 1 [14 19] 3,WM KO2, SE ATV X AS 8+9, :YH SDF 1O,Z AMI 1~2 HZD O, MSCs Z AMI 1~2./ 1.O, O8+9, 56L 1, MSC () AMI 2~3 `(\`( MSCO : Z O` (), Z SDF 1 : @ [ (\Q, ]^./`(()OIJ = `O]^34 4 23 WM_`O * a (5 10 5 MSCs/kg), ' :,b over the wirec M FG % over the wirec M F G % 3]: 1)MSC' 24h ^ ` FG PCI( c PCI) 2) over the wirec M Z _O FG JK 8 O b,1 K MSC 10mL, 3 10min ',_ 3~4mL 2~3min 5 4526 1)> ]? abc1 2) ()*+,-' C./:AMI 2~5 UCG a ]-., Z\ b, +,--.E' (&-. Y B' MSC, ` 10~14d;Z MSC ' 3 '+,-B`*,' 24h $' ( 6 ]M =,^ F G, ] _O 71 FG./ 3)TUVWX34:> ]( <, Z W WX, ATUVWX, TUVWX I,&ab 20mg/d a +,-./,./ 3./ 4 1 TUVWX 80mg/d, ab 20mg/d 4)!"01 :WM!"^ & c 1ab01 MSCs AMI 2~3 _O FG./;TUVWXZ < _ &J 2 Ob 6 5789 6 1 :;57 & MSC./ 12 = ; (LVEF,MRI )D `O8E
294 Basic&ClinicalMedicine 2017 37(3) 6 2 ;57 & MSC./ 12 =# (EDd,ESd,EDV, ESV,MRI Q)D `O8E ; MSC./ 12 (SPECT: S MRI )D `O8E ; MSC./ 12 56 ( PET )D `O8E ; MSC./ 1 1 : 12 ` = : 71; ^- IL 4,IL 6, IL 10,TNF α,hs CRP,SOD: MDA,NO,NT prob NP,SDF 1,CXCR4)D `O8E 6( MSC./ 6 : 12 S (MACE):^ ^ ; ; : 7 8 " O <2 MSC 01MNO S=, [ N :N 4PaO, HP [QR [2] / ]'O S S= # MSCO01 `, I\` MSC01`, 5 MSC01 MSC./ \`HP NO, : F7 <= S 4 1) ( 01C _ \`, ( G ; ) : F, ` 2) HM! ( 01C _ \`, ` 3)F7 MSC./ 1 1 3 6: 12 \ `,, ` 4) F ( 01C _ 6: 12 `\` 5) <= ;ab(wbc RBC Hb PLT): ( 01 C _ 1 ab(,-,- ): ( 01C _ 1 # ab + ;: ( 01C _ 1 EP ( ]* ; ;N): ( 01C _ 1 (CK CK MB TNT/TNI): 01C _ 6: 12 `\` ; = : ^ - (IL 4 IL 6 IL 10 TNF α hs CRP SOD: MDA NO NT probnp SDF 1 CXCR4): _ 1 : 1 `\` 6)MACE( ^ ^ ; ; : ) ( 01C./ 1, C _ 1 7) S C S ( 01C./ 1, C _ 1 8 <=./ 3d ( ):./ 12, (MRI) @ (PET) @! (SPECT) & O NO W :; ^,./ 1 : 1 `; = C (IL 4,IL 6,IL 10,TNF α,hs CRP, SOD: MDA,NO,NT probnp,sdf 1,CXCR4) ^ -O8E;./ 3 6: 12 \` ab c: Z _( S=, C` c0 >? %: [1]SmithSJ.Reducingtheglobalburdenofischemicheartdis easeandstroke:achalengeforthecardiovascularcommu nityandtheunitednations[j].circulation,2011,124: 278 279.
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