인체 양막과 지방조직에서 유래한 중간엽줄기세포의 특성 비교
COMPARISON WITH HUMAN AMNIOTIC MEMBRANE- AND ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS
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초록
목적중간엽줄기세포는 면역거부반응이 적고 자가세포의 분리가 가능하여 세포치료를 위한 이상적인 줄기세포의 공급원로 간주되고 있다. 양막에 중간엽줄기세포가 존재함이 보고되었으나, 이들 세포가 다른 조직에서 유래한 중간엽줄기세포와의 차이는 명확하게 밝혀져 있지 않다. 본 연구는 인체 양막유래 중간엽줄기세포와 지방조직유래 중간엽줄기세포의 특성을 비교분석하고자 하였다. 연구방법효소처리에 의해 분리 배양한 인체 양막유래 중간엽줄기세포와 지방조직유래 중간엽줄기세포의 특성을 세포성장, 표면항원발현, 세포분화능, 종양증식능 및 유전자발현을 통하여 비교하였다. 결과인체양막유래 중간엽줄기세포는 지방조직유래 중간엽줄기세포와 유사한 세포형태, 증식속도 및 표면항원의 발현양상은 나타내었으나,sonic hedgehog신호억제제인 cyclopamine은 양막유래 중간엽줄기세포만의 증식을 억제하였고 지방유래 중간엽줄기세포에 비해 낮은 지방세포 및 골모세포로의 분화능을 나타내었으며, nude mouse에 이식한 폐암세포의 증식촉진작용에 있어서 양막유래 중간엽줄기세포가지방조직유래 중간엽줄기세포보다 약한 효과를 나타냈었다. 또한, microarray로 측정한 유전자 발현양상에서 발달과 분화관련 유전자의유의한 발현차가 확인되었다. 결론이러한 결과는 양막유래 중간엽줄기세포와 성체조직유래 지방중간엽줄기세포 간의 특성차이를 밝힘으로서 임상적용목적에 따라 다양한조직에서 분리한 중간엽줄기세포를 사용하는 것이 줄기세포를 이용한 세포치료에 도움이 될 수 있다는 것을 제시한다.
Abstract
Objective Mesenchymal stem cells (MSC) have been considered as an ideal source of stem cells because of low immunogenicity and availability of autologous cells. Although it has been reported that amniotic membrane contains MSC, the difference between amniotic membrane–derived mesenchymal stem cells (AMSC) and MSC isolated from other tissues is still not clear. This study was designated to compare the characteristics and gene expression profi le of human AMSCs (hAMSC) and adipose tissue-derived mesenchymal stem cells (hADSC). Methods MSC were cultured from human amniotic membranes and adipose tissue by enzyme digestion. We compared the growth rate,surface marker expression, differentiation potential to adipogenic and osteogenic lineages, and gene expression of hAMSC with those of hADSC. Results hAMSC had growth rate and surface marker expression similar with hADSC. However, cyclopamine inhibited hAMSC proliferation in a dose-dependent manner without affecting hADSC proliferation. hAMSC showed lower differentiation potential to adipogenic and osteogenic lineages and lower in vivo tumor growth promoting effect in lung cancer cells xenotransplantion model of nude mouse than hADSC. Gene expression analysis using microarray revealed that many genes to be expressed differentially between hAMSC and hADSC are related to development and differentiation processes. Conclusion These fi ndings indicate that hAMSC have different characteristics with hADSC, and that to use MSC isolated from different sources according to therapeutic purposes may provide more promising results in clinical trials than general use of MSC from a specifi c source.
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