Effect of ex vivo culture conditions on immunosuppression by human mesenchymal stem cells

离体培养条件对人间充质干细胞免疫抑制的影响

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作者:Myoung Woo Lee, Dae Seong Kim, Somi Ryu, In Keun Jang, Hye Jin Kim, Jin Mo Yang, Doo-Hoon Lee, Soo Hyun Lee, Meong Hi Son, Hee Won Cheuh, Hye Lim Jung, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo

Abstract

A microarray analysis was performed to investigate whether ex vivo culture conditions affect the characteristics of MSCs. Gene expression profiles were mainly influenced by the level of cell confluence rather than initial seeding density. The analysis showed that 276 genes were upregulated and 230 genes downregulated in MSCs harvested at ~90% versus ~50% confluence (P < 0.05, FC > 2). The genes that were highly expressed in MSCs largely corresponded to chemotaxis, inflammation, and immune responses, indicating direct or indirect involvement in immunomodulatory functions. Specifically, PTGES and ULBP1 were up-regulated in MSCs harvested at high density. Treatment of MSCs with PTGES or ULBP1 siRNA reversed their inhibition of T-cell proliferation in vitro. The culture conditions such as cell confluence at harvest seem to be important for gene expression profile of MSCs; therefore, the results of this study may provide useful guidelines for the harvest of MSCs that can appropriately suppress the immune response.

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