역오팔 구조 지지체를 이용한 인간 지방 유래 줄기 세포의 연골 분화 촉진

Abstract

본 연구는 역오팔 지지체를 이용하여 인간지방유래 줄기세포의 연골 분화를 촉진하는 내용을 담고 있다. 비 다공성 구조를 가진 지지체에서 세포를 분화 시도하였을 경우 분화가 잘 촉진되지 않는 것에 비해 200 nm 정도의 균일한 구멍을 가지는 poly(D,L-lactide-co-glycolide)로 구성된 역오팔 지지체는 그 다공성 구조로 인하여 지지체의 내부까지 산소와 유기물의 수송을 가능하게 하여 지지체 내에서 어떤 유전적, 약물적 처리 없이 인간지방유래 줄기세포가 분화가 잘 되게 하는 것을 확인하였다. In this report, we present an inverse opal scaffold that can enhance the chondrogenic differentiation of human adipose-derived stem cells (hADSCs) without drug, gene, or cytokine supplement. Inverse opal scaffolds based on poly(D,L-lactide-co-glycolide) were formed with uniform <TEX>$200{\mu}m$</TEX> pores. Due to uniform pore sizes and well-controlled interconnectivity of inverse opal scaffold, hADSCs were allowed to distribute homogeneously throughout the scaffolds. As a result, high cell density culture with scaffold was possible. Since the hADSCs cultured in inverse opal scaffolds were subjected to limited supplies of oxygen and nutrients, these cells were naturally preconditioned to a hypoxic environment that stimulated the up-regulation of hypoxia-inducible factor-<TEX>$1{\alpha}$</TEX> (HIF-<TEX>$1{\alpha}$</TEX>). As a result, apoptotic activity of hADSCs until 3 weeks after initial cell seeding was significantly reduced and chondrogenic differentiation related molecular signal cascades were up regulated (transforming growth factor-beta, phosphorylated AKT, and phosphorylated p38 expression). In contrast, hADSCs cultured with small and non-uniform porous scaffolds showed significantly increased apoptotic activity with decreased chondrogenic differentiation. Taken together, inverse opal scaffold could potentially be used as an effective tool for improving chondrogenesis using stem cells.