ç¹çºæ§å€§è ¿éªšé å£æ»çã®æ°ããªã¡ã«ããºã ã解æ
ïœé»è¡æ§éªšå£æ»ã«ããã现èèåãæšçãšããæ°ããªæ²»çã¢ãããŒãã®å¯èœæ§ïœ
ãã€ã³ã
1.ç¹çºæ§å€§è ¿éªšé å£æ»çã¯ãå€§è ¿éªšé ã®è¡æµäœäžã«ããé»è¡(*1)æ§éªšå£æ»ã®ããã«è¡é¢ç¯
ãæ©èœã倱ãããé£ç ã§ãã
2.æ¬ç 究ã°ã«ãŒãã¯ä»åã®ç 究ã§ãç¹çºæ§å€§è ¿éªšé å£æ»çãšçŽ°èèå(*2)ã®é¢äžãæããã«
ãããŸããã
3.å€§è ¿éªšé ã®å£æ»å±€ã®ã¿ãªããã修埩移è¡å±€ã«ãããŠãèå现èã®èç©ãšÂ SASP(现èèå
ãé䌎åæ³çŸè±¡)(*3)ãçºçããŠããããšãåãããŸããã
4.é»è¡æ§éªšå£æ»ã¢ãã«ã«ãããŠãéè系幹现èå¹é€äžæž 液ã®æäžã«ãã现èèåãæå¶ãã
ã骚ã®å§æœ°ãäºé²ããããšã瀺ãããŸããã
5.ç¹çºæ§å€§è ¿éªšé å£æ»çã«ããã现èèåãæšçãšããæ°ããªæ²»çæ³ãæåŸ ãããŸãã
èŠæš
ãåœç«å€§åŠæ³äººæ±æµ·åœç«å€§åŠæ©æ§Â åå€å±å€§åŠå€§åŠé¢å»åŠç³»ç 究ç§æŽåœ¢å€ç§åŠã®å²¡æ¬ æå žå»å¡(ç 究åœæ)ãäžå³¶Â å®åœ°Â åææãä»é å²é ææãåç 究ç§é¡é¡é¢å€ç§åŠã®æ¥æ¯ è±æŽÂ ææãå倧åŠå»åŠéšéå±ç é¢æ¯ç§å£è å€ç§ã®é äº éœÂ å©æãã®ç 究ã°ã«ãŒãã¯ãç¹çºæ§å€§è ¿éªšé å£æ»çã«çŽ°èèåãé¢äžããŠããããšãæ°ãã«çºèŠããŸããã
ç¹çºæ§å€§è ¿éªšé å£æ»çã¯ãå€§è ¿éªšã®éªšé éšã®è¡æµã®äœäžã«ããå£æ»ã«é¥ããå£æ»ãã骚çµç¹ã朰ããããšã§è¡é¢ç¯æ©èœã倱ãããé£æ²»æ§çŸæ£ã§ãããã®åå ã¯æ確ã§ã¯ãããŸããã
æ¬ç 究ã°ã«ãŒãã¯ãå€§è ¿éªšé å£æ»çæ£è ããæè¡æã«æåºãã骚é ã®åæãè¡ãããšã§ã骚é å éšã®å¥åžžå±€ãšå£æ»å±€ã®éã®ç§»è¡å±€ã«èå现èã®èç©ããŠããããšãæããã«ããŸãããããã«èå现èãççãåŒãèµ·ããæ§ã ãªå åãæŸåºãã SASP ãšåŒã°ããçŸè±¡ãåŒãèµ·ãããå€§è ¿éªšé å£æ»çã®ç§»è¡å±€ã«ãã®Â SASP å åãååšããããšãèªããŸãããé»è¡æ§éªšå£æ»ããŠã¹ã¢ãã«ãçšããå®éšçµæã§ã¯ã现èèåãæããããšã«ãã骚ã®å§æœ°ãäºé²ããããšã瀺ãããŸããã
æ¬ç 究ã®ææã«ãããç¹çºæ§å€§è ¿éªšé å£æ»çã«å¯ŸããŠçŽ°èèåãæ°ããªæ²»çæšçãžãšãªãåŸãããšãžã®èšåºå±éãæåŸ ãããŸãã
èæ¯
ãç¹çºæ§å€§è ¿éªšé å£æ»çã¯ãå€§è ¿éªšã®éªšé éšã®é»è¡ã«ãã骚å£æ»ã«çããŠãå£æ»ããå€§è ¿éªšé ã朰ããããšã§è¡é¢ç¯æ©èœã倱ãããåå äžæã®é£æ²»æ§çŸæ£ã§ã(å³1)ã
è¡é¢ç¯ã®å€åœ¢ã«è³ã£ãŠããŸããšæè¡ä»¥å€ã«æå¹ãªæ²»çãååšããŸãããæ¥æ¬åœå ã§ã¯æ¯å¹ŽçŽÂ 2,000~3,000 人ã®æ°èŠæ£è ãçºçããéã»å£®å¹Žã«å¥œçºããããå»åŠçã«ã瀟äŒåŠçã«åé¡ãšãªã£ãŠãããäºé²æ³ã®éçºã®ããåå 解æãæåŸ ãããŠããŸãã
è¿å¹Žãå 霢ã DNA æå·ã«åŒãèµ·ããããã现èèå(cellular senescence)ããåè硬åçãç³å°¿ç ãå€åœ¢æ§é¢ç¯çãã¢ã«ããã€ããŒåèªç¥çãªã©æ§ã ãªç æ°ã«é¢ãã£ãŠããããšãåããã泚ç®ãããŠããŸããæ¬ç 究ã°ã«ãŒãã§ã¯ã以åã«è¬å€é¢é£é¡éªšå£æ»ã«ãããŠçŽ°èèåã®é¢äžã解æããŸãã(Watanabe ãã2020)ã
ä»åãæ¬ç 究ã°ã«ãŒãã¯ãé»è¡æ§éªšå£æ»ã§ããç¹çºæ§å€§è ¿éªšé å£æ»çãšçŽ°èèåãšã®é¢ãããæ¢ãããšèããŸãããããã«çŽ°èèåãå¶åŸ¡ããã¢ãããŒãã«ãã£ãŠé»è¡æ§éªšå£æ»ãæ²»çã§ããã調æ»ããŸããã
ç 究ææ
ãç 究ã°ã«ãŒãã¯ãç¹çºæ§å€§è ¿éªšé å£æ»çãšèšºæããæ£è ããæè¡æã«æåºããå€§è ¿éªšé ã®è§£æãè¡ããŸããã骚é æšæ¬ããèå现èã瀺ã X-gal æè²ãè¡ã垯ç¶ã«æè²ã«ãããŸãã(å³Â 2)ã
å³Â 2. ç¹çºæ§å€§è ¿éªšé å£æ»çã®éªšé ã®Â X-gal æè²ãšÂ MRI ç»å
X-gal æè²ã«ããèå现èã瀺ã匷ãéè²(èµ€â²)ã垯ç¶ã«æè²ãããŠããŸããããã¯Â MRI T1匷調å low ãã³ãå (é»ã垯)ã瀺ã移è¡å±€ã«äžèŽããŠããŸãã
ããã®åž¯ã¯å€§è ¿éªšé å£æ»ã®å£æ»å±€ãšå¥åžžå±€ã®å¢çã«ãã移è¡å±€ãšäžèŽããŠããããšãåãããŸãããçµç¹åŠç解æãšéºäŒåçºçŸè§£æã§ã¯ãå£æ»å±€ã®ã¿ãªãã移è¡å±€ã«ã现èèåãèµ·ãã£ãŠããŠãSASP å åãå€ãçºçŸããŠããããšå€æããŸãã(å³Â 3)ã
å³Â 3. èå å ç«æè²
移è¡å±€ã«ã¯çŽ°èèåã®ä»£è¡šçããŒã«ãŒã®1ã€ã§ãã p16ink4aéœæ§çŽ°èãå€ãèªããããŸãã
ã次ã«ãæ¬ç 究ã°ã«ãŒãã¯çŽ°èèåå¶åŸ¡ã«ãã£ãŠéªšå£æ»ãæ²»çãããæ€èšŒããããã«ãçåŸÂ 12 é±ç®ã®ããŠã¹ã«å€§è ¿éªšã«æ é€ãéã£ãŠããè¡ç®¡ãçŒãæè¡ãè¡ãããšã§è¡æµãé絶ããããŠéªšå£æ»ãåŒãèµ·ããé»è¡æ§éªšå£æ»ããŠã¹ã¢ãã«ã«å¯ŸããŠãæè¡åŸÂ 24 æéåŸã«ããç±æ¥ã®éè系幹现èå¹é€äžæž 液(MSC-CM)(*4)ãæäžããŸãããé»è¡æè¡ã§ã¯èåé¢é£Î²ã¬ã©ã¯ãã·ããŒãŒã®æŽ»æ§ãäžæããŠããŸããããMSC-CM æäžã«ãã£ãŠæŽ»æ§ãæå¶ãã现èèåãå¶åŸ¡ãããããšã瀺ãããŸãã(å³Â 4)ã
å³Â 4. èåé¢é£Î²ã¬ã©ã¯ãã·ããŒãŒã®æŽ»æ§
é»è¡æè¡ãè¡ã£ãŠããªã control ãšæ¯ã¹ãŠãé»è¡æè¡è¡ãå¹é€æ¶²ã®ã¿(DMEM)ãæäžãããšçŽ°èèåãã¿ãšããMSC-CM æäžãããšçŽ°èèåãæå¶ãããŸããã
ãäžæ¹ã§ãMSC-CM ã«ã¯é»è¡ããã®éªšçŽ°èã®çŽ°èæ»ãæžããããšã¯ãããŸããã§ãããããã«ãé¢ããã骚圢æã®å埩ãæ©ãããããŠæè¡åŸ6é±çµéããæç¹ã§ãã€ã¯ãCTæ®åœ±è¡ããšÂ MSC-CM æäžããããŠã¹ã®éªšã¯å§æœ°ãé²æ¢ãããŠããŸãã(å³Â 5)ã
å³Â 5. ãã€ã¯ã CT
é»è¡æ§éªšå£æ»ã«ãã£ãŠéªšå§æœ°ãåŒãèµ·ããããŸããããMSC-CM æäžã«ãã£ãŠå§æœ°ãäºé²ãããŸããã
ä»åŸã®å±é
ãä»åã®ç 究ææã«ãããå€§è ¿éªšé ã®é»è¡æ§éªšå£æ»ã§ããç¹çºæ§å€§è ¿éªšé å£æ»çãšçŽ°èèåã®é¢äžããŠããããšã瀺ãããããã«é»è¡æ§éªšå£æ»ã®çŽ°èèåãå¶åŸ¡ããããšã§éªšå§æœ°ãé²æ¢ããããšã瀺ããŸããã
å€§è ¿éªšé 骚å£æ»çã§ã¯éªšé ã®å§æœ°ãé²ãããšãæ²»çç®æšãšãªããããæ¬ç 究ã®ããŠã¹ã®å®éšã§å§æœ°ãæããããããšã¯éèŠãšèããŸãã
å°æ¥çã«ã¯ãæ¬ç 究ææã骚å§æœ°äºé²ã®æ°ããªæ²»çæŠç¥ã®æäŸãžãšã€ãªããæè¡ãåé¿ã§ããããã«ããŠããããšãæåŸ ãããŸãã
çšèªèª¬æ
*1) é»è¡ : è¡æµãäžæçãŸãã¯æ°žç¶çã«é»ãŸããããšãé»è¡ããããšçµç¹ã¯å£æ»ããŸãã
*2) 现èèå : 现èãæ§ã ãªåå ã«ãã修埩äžå¯èœãªÂ DNA æå·ããããããšã§èªå°ããã
äžå¯éç现èå¢æ®åæ¢çŸè±¡ã§ãã
*3) SASP(Senescence-Associated Secretory Phenotype) : 现èèåé䌎åæ³çŸè±¡ã
èå现èãççæ§ãµã€ãã«ã€ã³ã现èå€ãããªãã¯ã¹åè§£é µçŽ ãªã©æ§ã ãªåæ³å åã
æŸåºããçŸè±¡ã§ãã
*4) éè系幹现èå¹é€äžæž 液 : éè系幹现èã¯äœæ§å¹¹çŽ°èã®1ã€ã§éªšçŽ°èãè»éªšçŽ°èãèèª
现èã«ååããããšãã§ãã现èã§ããéè系幹现èå¹é€äžæž 液ã¯éè系幹现èã
å¹é€å¢æ®ããããã«å©çšããå¹é€æ¶²ã®äžæŸã¿æ¶²ã§ãããã®ãªãã«ã¯çç掻æ§ç©è³ªãå€
ãå«ãŸããŠãæççäœçšããããšãããŠããŸãã