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1. °³¿ä
¿À´Ã³¯, ¿©·¯ °¡Áö ¿øÀε鿡 ÀÇÇÑ °£¿° ¹× °£°æº¯Áõ¿¡ ´ëÇÏ¿© ¾à¹°Ä¡·á°¡ ÀÌ·ç¾îÁö°í ÀÖÀ¸¸ç ¾à¹°Ä¡·á°¡ ¾î·Á¿î °æ¿ì ±ÙÄ¡Àû °£À̽ÄÀÌ ½ÃÇàµÇ°í ÀÖ´Ù. ±×·¯³ª ¾à¹°¿¡ ´ëÇÑ Ä¡·áÀúÇ×¼ºÀ̳ª °£ÀÌ½Ä °ø¿©ÀÚÀÇ ºÎÁ·À¸·Î ÀÎÇÑ »õ·Î¿î Ä¡·á¹ýÀÇ Çʿ伺ÀÌ ´ëµÎµÇ°í ÀÖ´Ù. ¼±ÇàµÈ µ¿¹°½ÇÇè ¸ðµ¨¿¡¼, »ç¿°Èź¼Ò·Î À¯µµµÈ °£°æº¯ÁõÀÌ ÀÖ´Â ¸¶¿ì½º¿¡ °ñ¼ö¼¼Æ÷ ÁÖÀÔ ÈÄ, Ç÷ûÇÐÀû, Á¶Á÷ÇÐÀû ¼Õ»óÀÌ ÇöÀúÇÏ°Ô °¨¼ÒÇÒ »Ó¸¸ ¾Æ´Ï¶ó »ýÁ¸À²À» Áõ°¡½ÃÄ×´Ù´Â º¸°í°¡ ÀÖ¾ú´Ù (Sakaida, et al., 2004). ÀÌ·¯ÇÑ °á°ú´Â ÁÖÀÔÇÑ °ñ¼öÀ¯·¡ ¼¼Æ÷°¡ ÀÌ½Ä ¸¶¿ì½º °£³»·Î À̵¿ÇÑ ÈÄ, »ç¿°Èź¼Ò·Î ¼Õ»ó¹ÞÀº °£¿¡¼ ±â´ÉÀû °£¼¼Æ÷·Î Á÷Á¢ ºÐÈÇÏ¿© À籸¼ºµÊÀ¸·Î½á ÀÌ¿Í °°Àº È¿°ú¸¦ ³ªÅ¸³½´Ù°í »ý°¢ÇÒ ¼ö ÀÖ´Ù(Kuo, et al., 2008). »Ó¸¸ ¾Æ´Ï¶ó, ÀÓ»ó º¸°í¿¡¼µµ µ¿¹°½ÇÇè°ú À¯»çÇÏ°Ô ¾ËÄڿüº, ±«»çÈļº, ÀÚ°¡¸é¿ª¼º °£Áúȯ ȯÀڵ鿡°Ô ÀÚ½ÅÀÇ °ñ¼ö¼¼Æ÷(whole bone marrow cells)¸¦ À̽ÄÇÏ¿© °£±â´ÉÀÇ °³¼±, °£ Áõ½ÄÇ¥ÁöÀÇ Áõ°¡ ¹× »îÀÇ Áú Çâ»ó µîÀÇ ±àÁ¤ÀûÀÎ °á°úµéÀÌ º¸°íµÇ¾ú´Ù (Park, et al., 2013, Spahr, et al., 2013, Amin, et al., 2013). ÀÌó·³ °£Àç»ý Ä¡·áºÐ¾ß¿¡¼ °£°æº¯Áõ¿¡ ´ëÇÑ °ñ¼ö¼¼Æ÷ Ä¡·á´Â »ó´çÈ÷ ¸Å·ÂÀûÀÎ Ä¡·á¹æ¹ýÀÌÁö¸¸ ´ë´Ù¼öÀÇ ¿¬±¸¿¡¼ ÀÚ°¡ °ñ¼ö¼¼Æ÷ ÁÖÀÔÀÇ È¿°ú¿Í ¾ÈÀü¼º¿¡ ÁÖ¸ñÇÏ¿´À» »Ó, ¾ÆÁ÷±îÁö °ñ¼ö¼¼Æ÷ ³» ¾î¶² ¼¼Æ÷°¡ °£°æº¯ÁõÀ» ¿ÏȽÃÅ°´ÂÁö¿¡ ´ëÇؼ´Â ¸íÈ®È÷ ¹àÇôÁ® ÀÖÁö ¾Ê°í ÀÖ´Ù. µû¶ó¼ º» º¸°í¿¡¼´Â °£°æº¯ÁõÀÇ ±âÀü¿¡ ´ëÇÏ¿© °£´ÜÈ÷ »ìÆ캸°í, °ñ¼ö¼¼Æ÷¿¡ ¾î¶² Ư¼ºÀ» °®´Â ¼¼Æ÷µéÀÌ Á¸ÀçÇÏ¿© °£°æº¯ÁõÀ» ¿ÏȽÃÅ°´ÂÁö ±× ±âÀü¿¡ ´ëÇØ ÀÚ¼¼È÷ »ìÆ캸°íÀÚ ÇÑ´Ù.
2. °£°æº¯Áõ (Liver cirrhosis)ÀÇ ±âÀü
°£°æº¯Áõ(cirrhosis)Àº °£¼¶À¯È(fibrosis)ÀÇ Áß½ÉÀÌ µÇ´Â ¿øÀÎ ¼¼Æ÷·Î ¾Ë·ÁÁø °£¼º»ó¼¼Æ÷(hepatic stellate cells)ÀÇ È°¼ºÀ¸·Î ÀÎÇØ ºÐºñµÇ´Â °úµµÇÑ ¼¼Æ÷¿Ü ±âÁú(extracellular matrix; ECM)ÀÇ ÃàÀû¿¡ ÀÇÇØ ÀÏ¾î³´Ù°í ¾Ë·ÁÁ® ÀÖ´Ù (Hernandez-Gea V, et al., 2011). ÀϹÝÀûÀ¸·Î °£¼º»ó¼¼Æ÷´Â °£¼¼Æ÷¿Í µ¿¾ç³»ÇǼ¼Æ÷(sinusoidal endothelial cells) »çÀÌ µð¼¼°(Space of Disse)¿¡ À§Ä¡ÇÏ¿© ÀÖ´Ù(Friedman SL, 2008). Á¤»ó»óÅ¿¡¼ ÈÞÁö±âÀÇ °£¼º»ó¼¼Æ÷´Â ¼¼Æ÷Áú ³»¿¡ ·¹Æ¼³î(Vitamin A)À» ´Ù·® ÇÔÀ¯ÇÏ°í ÀÖ´Â Áö¹æ±¸µéÀ» °¡Áö°í ÀÖÁö¸¸ È°¼ºÈ°¡ µÇ¸é ·¹Æ¼³î Áö¹æ±¸µéÀ» ÀÒ¾î¹ö¸®°í ±Ù¼¶À¯¾Æ¼¼Æ÷(myofibroblast-like cell)¿Í °°Àº ¸ð¾çÀ¸·Î º¯ÇÏ¸é¼ ¸¹Àº ¾çÀÇ Äݶó°Õ ¼¶À¯µéÀ» ºÐºñÇÏ°í ¥á-smooth muscle actin¸¦ ¹ßÇöÇÔÀ¸·Î½á °£¼¶À¯È¸¦ ÃÊ·¡ÇÏ°Ô µÈ´Ù(±×¸² 1). °£ ¼Õ»óÀÌ ÀÌ·ç¾îÁö¸é¼, °£¼º»ó¼¼Æ÷´Â transforming growth factor-¥â1(TGF-¥â1), ÀÎÅÍ·ùŲ(interleukin)-6(IL-6) ¹× monocyte chemoattractant protein-1(MCP-1)°ú °°Àº »çÀÌÅäÄ«ÀÎ µîÀ» ºÐºñÇÏ¸ç °£³» ¸é¿ª¼¼Æ÷µéÀ» È°¼ºÈ½ÃÅ´À¸·Î½á °£¼¶À¯È¸¦ ´õ¿í ÃËÁø½ÃŲ´Ù(Thompson K, et al., 1998, Radaeva S, et al., 2007). ´ëÇ¥ÀûÀ¸·Î È°¼ºÈµÈ °£¼º»ó¼¼Æ÷µéÀº Á÷Á¢ °£³» Ç׿øÁ¦½Ã¼¼Æ÷·Î¼ ±â´ÉÀ» ÇÏ¿© °£³» T ¼¼Æ÷, ÀÚ¿¬»ìÇؼ¼Æ÷(NK cells), ÀÚ¿¬»ìÇØ T ¼¼Æ÷(NK T cells) µî °£¼Õ»ó°ú °ü·ÃµÈ ¿©·¯ ¿°Áõ¼¼Æ÷µéÀ» È°¼ºÈ½ÃÅ°´Âµ¥ °ü¿© Çϱ⵵ ÇÑ´Ù(Winau, et al., 2007, Radaeva S, et al., 2006). °á°úÀûÀ¸·Î °£¼¶À¯È¿¡ Áß¿äÇÑ ¿ªÇÒÀ» ÇÏ´Â °£¼º»ó¼¼Æ÷ÀÇ È°¼º¾ïÁ¦ ¹× »ç¸êÀÌ °£°æº¯À» È£Àü½ÃÅ°´Âµ¥ °¡Àå Áß¿äÇÑ Å¸°ÙÀ¸·Î ¿©°ÜÁö°í ÀÖ´Ù.
±×¸² 1. °£µ¿¾çÇ÷°ü³» À§Ä¡ÇÏ°í ÀÖ´Â °£¼º»ó¼¼Æ÷µé(È»ìÇ¥; Ǫ¸¥»ö)Àº ÈÞÁö±â ·¹Æ¼³îÀ» °¡Áö°í ÀÖÀ¸³ª °£¼Õ»óÀÌ ½ÃÀ۵Ǹé Áõ½Ä°ú µ¿½Ã¿¡ ¸¹Àº ¼¼Æ÷¿Ü±âÁúÀ» ºÐºñÇÏ¿© °£¼¶À¯È¸¦ À¯µµÇÔ(Physiol Rev. 2008 Jan;88(1):125-72).
3. ÀÚ°¡°ñ¼ö¼¼Æ÷(autologous bone marrwo cell)¸¦ ÀÌ¿ëÇÑ °£ Áúȯġ·á ¿¬±¸
Áö³ ¼ö½Ê ³â°£ ÀÓ»óÀû ȤÀº ½ÇÇèÀû ¿¬±¸º¸°í¿¡ ÀÇÇϸé ÀÚ°¡°ñ¼ö¼¼Æ÷ ÁÖÀÔ¼ú (infusion therapy of autologous bone marrow cell)Àº °£Àç»ý, °£¼Õ»ó ¹× °£°æº¯Áõ¿¡ È¿°úÀûÀ¸·Î ¾Ë·ÁÁ® ¿Ô¾ú´Ù. ÁÖ·Î ÁÖÀÔµÈ °ñ¼ö¼¼Æ÷µéÀÌ °£¼¼Æ÷·Î Á÷Á¢ ºÐȸ¦ Çϰųª, °£Àü±¸¼¼Æ÷µé(progenitor cell)ÀÇ Áõ½ÄÀ¯µµ ¹× °£³» ÃàÀûµÈ ¼¼Æ÷¿Ü±âÁú(ECM)À» ºÐÇؽÃÅ´À¸·Î °£ Áúȯ¿¡ º¸È£ ÀÛ¿ëÀ» ÇÏ´Â °ÍÀ¸·Î ¾Ë·ÁÁ® ¿Ô´Ù(Petersen et al., 1999, Sakaida I et al., 2004, Terai S et al., 2006). ±×·¯³ª °ñ¼ö ³»¿¡ Á¸ÀçÇÏ´Â ¼¼Æ÷µéÀÇ ´Ù¾ç¼ºÀ¸·Î ÀÎÇÏ¿© ¾î¶² ¼¼Æ÷µéÀÌ ÀÌ·¯ÇÑ ÀÛ¿ëµéÀ» ÇÏ´ÂÁö¿¡ ´ëÇÑ ±âÀüÀÌ ¾ÆÁ÷±îÁö ºÒºÐ¸íÇÑ »óÅÂÀÌ´Ù.
ÃÖ±Ù ¿¬±¸µé¿¡ ÀÇÇÏ¸é °£¼¶À¯ÈÀÇ ÁÖ¿ä¼¼Æ÷ÀÎ °£¼º»ó¼¼Æ÷µéÀÌ Äݶó°Õ°ú °°Àº ¼¼Æ÷¿Ü±âÁú(ECM) ºÐºñ ±â´ÉÀÌ¿Ü¿¡ ¸é¿ª¼¼Æ÷µé°úÀÇ »óÈ£ÀÛ¿ë¿¡ °üÇÑ º¸°í°¡ ¸¹ÀÌ µÇ¾î¿À°í ÀÖ°í, ¿¹¸¦ µé¸é T ¼¼Æ÷¿Í NK ¼¼Æ÷µéÀ» È°¼ºÈ½ÃÅ°°Å³ª CD11b+Gr1+ °ñ¼öÀ¯·¡¾ïÁ¦¼¼Æ÷ (myeloid-derived suppressor cell; MDSC) ¹× CD4+CD25+Foxp3+ regulatory T ¼¼Æ÷(Treg)µéÀÇ À¯µµ¿¡ °ü¿©¸¦ ÇÏ°í ÀÖ´Ù´Â °ÍÀÌ º¸°í°¡ µÇ¾ú´Ù. µû¶ó¼ ÁÖÀÔµÈ ÀÚ°¡°ñ¼ö¼¼Æ÷µé Áß Æ¯Á¤ °ñ¼ö¼¼Æ÷µéÀÌ °£¼º»ó¼¼Æ÷¿Í »óÈ£ÀÛ¿ëÀ» ÅëÇؼ °£¼¶À¯È°¡ ¿Ï鵃 ¼ö ÀÖ´Ù´Â °¡¼³ÀÌ ¼º¸³ÇÏ°Ô µÈ´Ù.
4. ÀÚ°¡°ñ¼ö¼¼Æ÷¸¦ ÀÌ¿ëÇÑ °£ Áúȯ Ä¡·á±âÀü
°ñ¼ö ³»¿¡ Á¸ÀçÇÏ´Â ¼¼Æ÷µéÀº ´Ù¾çÇÑ Áٱ⼼Æ÷(stem cell) ±ºµé°ú ´ÜÇÙ±¸°è¿(monocytic) ¹× °ú¸³±¸°è¿(granulocytic)ÀÇ Àü±¸¼¼Æ÷µé·Î ÀÌ·ç¾îÁ® ÀÖ´Ù(Biermann H, et al., 1999). ƯÈ÷ ¿ì¸®°¡ ÁÖ¸ñÇÏ´Â ¼¼Æ÷µéÀº °ñ¼ö ³»¿¡ Á¸ÀçÇÏ´Â °ñ¼öÀ¯·¡¾ïÁ¦¼¼Æ÷µé(MDSC)·Î ÁÖ·Î °ñ¼öÀü±¸¼¼Æ÷µé(myeloid progenitor cells)°ú ¹Ì¼º¼÷ °ñ¼ö¼¼Æ÷µé(immature myeloid cells)·Î ÀÌ·ç¾îÁ® ÀÖ´Ù. °ñ¼öÀ¯·¡¾ïÁ¦¼¼Æ÷µé(MDSC)ÀÇ °æ¿ì ±×¸² 2¿Í °°ÀÌ Gr1°ú CD11b¸¦ ¹ßÇöÇÏ´Â ¼¼Æ÷µé·Î½á ÁÖ·Î ¾ÏȯÀڵ鿡¼ ¿°Áõ¼¼Æ÷µé(ƯÈ÷ Ç׾ϼ¼Æ÷µé)À» ¾ïÁ¦ÇÏ´Â ±â´ÉÀ» Çϸç, ÀÌµé ¼¼Æ÷µéÀº ´Ù½Ã Å©°Ô 2°¡Áö ÁÖ¿ä ±×·ìÀ¸·Î ±¸ºÐµÇ´Âµ¥, CD11b+Ly6G+Ly6Clow granulocytic MDSC¿Í CD11b+Ly6G-Ly6Chigh monocytic MDSCÀ¸·Î ³ª´²Áø´Ù(Gabrilovich DI and Nagaraj S, 2009, Youn JI, et al., 2010).
±×¸² 2. ´Ù¸¥ ÇüÅÂÀÇ MDSCµé°ú ÀÌµé ¼¼Æ÷µéÀÇ T ¼¼Æ÷ ¾ïÁ¦±âÀü(Nat Rev Immunol. 2009 Mar;9(3):162-74).
ÀÌµé °ñ¼öÀ¯·¡¾ïÁ¦¼¼Æ÷µé(MDSC)ÀÇ ÀüÇüÀûÀΠƯ¡Àº arginase-1, iNOS ¹× ROS¸¦ ºÐºñÇÔÀ¸·Î ÀÎÇØ T¼¼Æ÷¿Í °°Àº ¸é¿ª¼¼Æ÷µé¿¡ ´ëÇÑ ¾ïÁ¦±â´ÉÀ» °®´Â´Ù´Â °ÍÀÌ´Ù(Ostrand-Rosenberg S, et al., 2010, Gabrilovich DI, et al., 2009). ¶ÇÇÑ ¿°ÁõÀ» ¾ïÁ¦½ÃÅ°´Â Treg¼¼Æ÷µéÀÇ À¯µµ¿¡µµ °ü¿©¸¦ ÇÏ¿© TGF-¥â1°ú ÀÎÅÍ·ùŲ-10(IL-10)ÀÇ ºÐºñ¸¦ ÃËÁø½ÃÅ°¸ç, ÀÌ·¸°Ô ºÐºñµÈ ÀÎÅÍ·ùŲ-10Àº Ç׿°ÁõÀÛ¿ë »Ó¸¸ ¾Æ´Ï¶ó ƯÀÌÀûÀ¸·Î °£¼º»ó¼¼Æ÷µéÀÇ È°¼º¾ïÁ¦¿¡µµ °ü¿©¸¦ ÇÏ°í ÀÖ´Ù°í ¾Ë·ÁÁ® ÀÖ´Ù(Hernandez-Gea et al., 2011, Thompson K et al., 1998). ÀÌ·¯ÇÑ º¸°íµéÀ» Á¾ÇÕÇÏ¿© º¼ ¶§, ¿ì¸®´Â °ñ¼ö³» Á¸ÀçÇÏ´Â MDSC À¯»ç ¼¼Æ÷µéÀÌ °£³»·Î À̵¿ÇÏ¿© °£¼º»ó¼¼Æ÷¿Í »óÈ£ÀÛ¿ëÀ» ÇÑ ÈÄ ÀÎÅÍ·ùŲ-10À» ºÐºñÇÏ¿© °£¼º»ó¼¼Æ÷ÀÇ È°¼ºÀ» ¾ïÁ¦ÇÒ °ÍÀ̶ó´Â °¡¼³À» ¼¼¿ì°í ¿¬±¸¸¦ ½Ç½ÃÇÏ¿´´Ù.
±×¸² 3A¿¡¼¿Í °°ÀÌ ÁÖÀÔµÈ °ñ¼ö¼¼Æ÷µé(³ì»öÇü±¤)Àº ƯÀÌÀûÀ¸·Î È°¼ºÈµÈ °£¼º»ó¼¼Æ÷µé(ºÓÀº»ö) ÁÖÀ§¿¡¼¸¸ °üÂûÀÌ µÇ¸ç ÁÖÀÔ ÈÄ 24½Ã°£ ³»¿¡ °£¼¶À¯È°¡ È£Àü(±×¸² 3B; Äݶó°Õ ħÂøÀÌ ÇöÀúÈ÷ ÀúÇÏ)µÇ´Â °ÍÀÌ °üÂûµÇ¾ú´Ù. ¶ÇÇÑ °£³» ¿°ÁõÀ» ¾ïÁ¦ÇÏ´Â TregÀÇ ºÐÆ÷°¡ ÇöÀúÇÏ°Ô Áõ°¡ÇÏ¿´À¸¸ç(±×¸² 3C) Áõ°¡µÈ TregÀ¸·Î ÀÎÇÏ¿© MCP-1À̳ª ÀÎÅÍ·ùŲ-6¿Í °°Àº ¿°Áõ¼º »çÀÌÅäÄ«ÀÎÀÇ ¹ßÇöÀº °¨¼ÒµÇ¾úÀ¸¸ç, ÀÌ¿Í ¿¬µ¿µÇ¾î °£³» ¿°Áõ¼º ´ë½Ä±¸µéÀÇ ºÐÆ÷µµ 24½Ã°£Â°¿¡ À¯ÀÇÇÏ°Ô °¨¼ÒÇÏ¿´´Ù(Suh YG, et al., 2012). ´ÙÀ½À¸·Î´Â ÁÖÀÔµÈ °ñ¼ö¼¼Æ÷µé ºÐ¼®¿¡¼ Treg°ú À¯»çÇÏ°Ô ¿°ÁõÀ» ¾ïÁ¦ÇÏ´Â ÀÎÅÍ·ùŲ-10ÀÌ °ÇÏ°Ô ºÐºñµÇ°í ÀÖ´Â °ÍÀÌ °üÂûµÇ¾úÀ¸¸ç À̵éÀº °¢°¢ CD11b+Gr1highF4/80-¿Í CD11b+Gr1+F4/80+ ¼¼Æ÷µé·Î ¹àÇôÁ³À¸¸ç Èï¹Ì·Ó°Ôµµ CD11b+Gr1highF4/80- ¼¼Æ÷µéÀº granulocytic MDSC¿Í CD11b+Gr1+F4/80+ ¼¼Æ÷µéÀº monocytic MDSC¿Í °°Àº ÇüÅÂÀÇ ¼¼Æ÷µé·Î ¹àÇôÁ³´Ù(±×¸² 4).
±×¸² 3. °ñ¼ö¼¼Æ÷µéÀÇ °£¼º»ó¼¼Æ÷¿ÍÀÇ »óÈ£ÀÛ¿ë ¹× TregÀÇ ºÐÆ÷ Áõ°¡·Î ÀÎÇÑ Ç×¼¶À¯È ±â´É
±×¸² 4. ÁÖÀÔµÈ °ñ¼ö¼¼Æ÷µéÀÇ ÀÎÅÍ·ùŲ-10ÀÇ ¹ßÇö°ú MDSC¿Í À¯»çÇÑ ¸¶Ä¿¸¦ ¹ßÇöÇÔ.
ÀÌ·¯ÇÑ ±âÀüÀº in vitro ¼¼Æ÷¼öÁØ ½ÇÇè¿¡¼µµ Áõ¸íµÇ¾ú´Âµ¥, ¸¶¿ì½ºÀÇ °ñ¼ö¼¼Æ÷¿Í ¸¶¿ì½º °£¼º»ó¼¼Æ÷µé(±×¸² 5A) ±×¸®°í Àΰ£ °ñ¼ö¼¼Æ÷(±×¸² 5B)µé°ú Àΰ£ °£¼º»ó¼¼Æ÷ÁÖ(LX-2 ¹× hTERT)µé°úÀÇ °øµ¿¹è¾ç¿¡¼µµ °ñ¼ö¼¼Æ÷µéÀÇ ÀÎÅÍ·ùŲ-10ÀÇ ¹ßÇöÀÌ ÇöÀúÇÏ°Ô Áõ°¡µÇ¾ú°í, ÀÌµé °ñ¼ö¼¼Æ÷µéÀÇ ÀÎÅÍ·ùŲ-10ÀÇ ¹ßÇö Á¤µµ´Â °£¼º»ó¼¼Æ÷µéÀÌ ºÐºñÇÏ´Â ·¹Æ¼³ëÀÍ»ê(retinoic acid)¿¡ ÀÇÇØ ´õ¿í ÃËÁøµÇ°í ÀÎÅÍ·ùŲ-6¿¡ ÀÇÇØ ¾ïÁ¦µÊÀ» È®ÀÎÇÏ¿´´Ù(Suh YG, et al., 2012). ÀÓ»ó½ÇÇè °á°ú¿¡¼µµ, °£°æº¯Áõ ȯÀÚ¿¡°Ô ÀÚ°¡°ñ¼ö¼¼Æ÷ ÁÖÀÔ ÈÄ¿¡ Ç÷û ÀÎÅÍ·ùŲ-10ÀÌ ÇöÀúÇÏ°Ô »ó½ÂÇÏ¿© µ¿¹°½ÇÇè ¹× in vitro ½ÇÇè°á°ú¿Í ºÎÇյǴ °á·ÐÀ» ¾òÀ» ¼ö ÀÖ¾ú´Ù(Suh YG, et al., 2012). »Ó¸¸ ¾Æ´Ï¶ó »ç¿°Èź¼Ò À¯µµ °£¼¶À¯È ¸¶¿ì½º ¸ðµ¨¿¡¼ colony stimulatory factor-1(CSF-1) À¯µµ °ñ¼ö ´ë½Ä¼¼Æ÷ ÁÖÀÔ ÈÄ¿¡ ÀÎÅÍ·ùŲ-10ÀÌ »ó½ÂµÊÀÌ º¸°íµÇ¾ú´Ù(Thomas JA, 2011).
±×¸² 5. ¸¶¿ì½º¿Í Àΰ£ °£¼º»ó¼¼Æ÷¿Í °ñ¼ö¼¼Æ÷µé ¸ðµÎ¿¡¼ »óÈ£ÀÛ¿ëÀÌ °üÂûµÊ.
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