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Biomaterials Research (2007) 11(3) : 91-95 <Review> Biomaterials Research 7 The Korean Society for Biomaterials w» s w š A Brief Review on Adipose Tissue-Derived Mesenchymal Stem Cells * Gun-Il Im* Š f e hœd Dept. of Orthopaedics, Dongguk University International Hospital ((Received July 19, 2007/Accepted August 1, 2007)) Adipose tissue can provide an abundant source of adult stem cells that may be used for cell therapy and tissue engineering. However, it is not confirmed whether adipose tissue can provide stem cells that have a potential for effective tissue regeneration equal to those from bone marrow. In this review are introduced the recent advances in the characterization, differentiation, and applications of adipose tissue-derived mesenchymal stem cells. Key words: Adipose tissue, Mesenchymal stem cell, Tissue engineering j, l. e f i l f igš f hf l Œ f Šf Š d f Œ Š Š f elš Šf Š. j hhš i f il f ŒŠ. j Š f f lš f Š j f Š hf d f f ƒ f i t ŒfŠ f eš lf h fl Š f. u h x Š f ilj ee f 4 l j j j Œ f lf f Š,, l ilf ŒŠ f Š CD73, CD90, CD105 f Šef lš CD45, CD14, CD11b, CD34, CD19, CD79a, HLA-DR f f Š. 1) j, h Œ, l, Œ il Š j l f f f f } f swš f ghf f esilf f. 2-3) wš f f swš ff Œ~, Šh ƒ, Œ f Š } rf ut f l i l Š f e Š. 4-5) *sf hf: gunil@duih.org l Š h lxš d f Œ f ff f. l (SVF, stromal vascular cell fraction)f f l ilf el Š (collagenase) s Š e Š Š l e l (ADSC, adipose tissue-derived stromal cell), l e j (ATMSC, adipose tissue derived mesenchymal stem cell)f SVF Š ilf Œ f Œf Š j f lf Œf Š f h d f xf. 6) u g l l l e j f ƒ, Œ x il Š f hd f h Š f Š.»» s p l e j il Š j f e Š f lš e f i l. f ff, l ilf i, ex,, i, l l Œ f f f f. 4,7-12) f f f f hf sw f sw e ll f f Œ f s 3,13) w e l f k f Œf 14) f l ilf Š Šh ex ƒ f f } g hf ƒ f l f. f l h sw l hh f tf f. 3) r f 91

92 f f l f hf f jg w Š il Œ f f el. h 15) l yl l f Œ Dulbecco s modified Eagle s medium f α-mem Š hf f Œ l rf. f 11) d f r h r f f lf f x. Š Œ lf 16) N-acetyl- L-cysteine, L-ascorbic acid 2-phosphate f x l j f g f l ~. l e 17) j e j Š lf l f elš h if gfff f f FGF-2 PDGFf fš d tl. 18) l e j f ehf lf Š l f f fdš ƒhilf f Œe hf x ŠdŠ. h FACS (fluorecence activated cell sorting) fdš l e j e j Š ehf lf 1% h f rf f f h. ƒ 11) j r l HLA-DRf f hf df f f lf l e j if f fd fff Š. 19)»» s y ƒ j l, e,,, ef ŒŠ f f f. Œ h ƒf h ff f d j ef ŒŠ f f h Œ (transdifferentiation) Š. l e j j ef d ef f, f ŒŠ f f r Œ (crossdifferentiation) Š. y l e j l f ŒŠ. f ŒŠ f Š l f ƒlf adiponectinf leptinf Š catecholaminef Š f l f ŠŠ lf l Œ. 10) l f f f d, Œ, i hh il f g (fistula) f Crohn f d eš fd f. ƒ 20) poly-lactic-co-glycolic acid sphere l Œ ~ j r ~ jfœlltf f f ilg e Š d f. 21) y f il Š f f h (precursor cells) d } Œ g f f f f l ilf ƒ edš. f g f g g i ŠŠ f g ff Š l e j f f hd f g f. l ilf sw e Œ rf f Œ f f h swš l e j Šl f STRO-1, CD106 Še f h, l h, lœ h, lf Œ h d Š f h f. 22) Š Š j Šl ef j Š d hf Œ f Š. 23) hff Œ h l l l gfff i f fdš f f f Œ ef j Š hfl Š. 24) f f h Š e Š Š f l e j hf f Œ f eš gi f r eš eš lš. u f Š f l ej f TGF-β dt h l f f TGF fšl fef BMP Š d TGF-β dtf l Š hf Œ f Šf. 25) h ff u Š gfff išf Š TGF-β BMP-7f iš hf Œ f f TGF-β IGF-If Š d Š Œ f l f edš fd f f (Figure 1). d f fš f Œ e Š f ff l gff BMP-6, BMP-7, FGF-2f f. 26-28) Šl Š Š l e j fš f hf Œ je g fš if Œ f f. 29) / (muscle, myocardium) y l e j IL-3. IL-6 ŠŠ t ~ f methylcellulose l Š f e Š Œ(phenotype) ƒfš lf l ŒŠ f. f Œ f hf f f 30) adrenaline acetylcholine g e e Š fš. k ŠŠ t f l j f Š f Œ, Œ Œ ƒfš l ff f r. 31,32) l e j (skeletal myoblast) ŒŠ ƒfš e l fdš f ƒ (myotube) Œ Š (striated muscle)f lf l ŒŠ f. f mdx mice (Duchenne f l k) f Š f ef g lff dystrophinef f r. l j 33) Biomaterials Research 2007

지방에서 유래한 간엽줄기세포에 대한 소고 93 Induction of chondrogenesis from adipose tissue -derived mesenchymal stem cell in a pellet culture ( 100 Safranin-O staining). The cellular differentiation and the degree of metachromasia increased with combined treatment of TGF-β2 (5 ng/ml) and BMP-7 (50 ng/ml) or with high dose of combined TGF-β2 (15 ng/ml) and IGF (500 ng/ml). Figure 1. 세포는 일반적으로 골수기원간엽줄기세포에 비하여 근육으로 분화능력이 전반적으로 약한 것으로 관찰되며 근육세포와의 직 접접촉이 분화에 필요하다. 혈관내피세포(Vascular endothelial cell)로의 분화 쥐에서 분리한 지방기원간엽줄기세포는 혈관형성의 능력을 가지고 있고 VEGF, HGF, placental growth factor, FGF등의 혈관형성에 관계된 유전자를 대량 분비한다. 골수줄기세포와 비 교하여 동등한 정도의 혈관 형성능력이 관찰되어 허혈성 질환 의 치료에 유용할 것으로 사료된다. 신경계(neuron)로의 분화 지방기원간엽줄기세포를 일반적인 신경유도조건하에서 배양하 면 신경계 분화인자인 type III β-tubulin을 분비하게 된다. 또한 더 복잡한 신경유도배지하에서 생쥐와 사람의 지방줄기세 포에서 glial fibrillary acidic protein(gfap)와 nestin, NeuN, intermediate filament M 등이 발현된다. 아직 그 작용기전 이 밝혀지지 않았지만 뇌졸종후 기능회복을 위하여 연구되고 34) 16,35-37) 38) 있다. 췌장섬세포(pancreas islet cell)로의 분화 사람의 지방기원간엽줄기세포는 activin-a, exendin-4, HGF, pentagastrin등의 분화인자를 쓸 경우 췌장섬세포로 분화할 수 있음이 밝혀졌다. 이 세포는 췌장섬세포의 분화에 관여하는 전사인자인 ISl-1, Pax-6, Ipf-1, Ngn-3 등을 표현한다. 또한 이렇게 분화된 세포는 췌장섬세포의 제일 중요한 기능인 insulin, glucagon, IGF 등의 호르몬을 분비하여 앞으로 사람의 제 1형 당뇨병에 세포치료로 이용될 수 있는 가능성이 제시되 고 있다. 간세포(hepatocyte)로의 분화 지방기원간엽줄기세포에 HGF(hepatocyte growthfactor), oncostatin M(OSM), DMSO를 처리할 경우 albumin과 αfetoprotein을 분비하는 간세포의 기능을 가진 세포로 분화할 수 있다. 이 분화된 세포들은 low-density lipoprotein을 흡 수하고 요소를 생산하는 등의 고도의 간세포기능도 가질 수 있 39) 40) 41) Vol. 11, No. 3

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