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乳糖酸共轭热凝胶中介导的间充质干细胞的肝源性支持分化

Hepatogenic Supported Differentiation of Mesenchymal Stem Cells in a Lactobionic Acid-Conjugated Thermogel.

作者信息

Moon Hyo Jung, Lee Hyun Jung, Patel Madhumita, Park Sohee, Chang Seo Hee, Jeong Byeongmoon

机构信息

Department of Chemistry and Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Korea.

出版信息

ACS Macro Lett. 2017 Nov 21;6(11):1305-1309. doi: 10.1021/acsmacrolett.7b00802. Epub 2017 Nov 7.

Abstract

To investigate the effect of receptor substrate of target cells on stem cell differentiation, lactobionic acid-conjugated poly[(propylene glycol)--(ethylene glycol)--(propylene glycol)]-poly(l-alanine) (LB-PLX-PA) was synthesized, and then thermogelling systems consisting of LB-PLX-PA and PLX-PA in a ratio of 0/100 (LB-0), 5/95 (LB-5), and 20/80 (LB-20) were constructed as an injectable three-dimensional scaffold toward hepatogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs). Modulus of LB-0, LB-5, and LB-20 increased to 500-800 Pa at 37 °C (gel) due to the heat induced sol-to-gel transition of the systems during which TMSCs were incorporated into the gel. Based on biomarker expressions and hepatic biofunctions of the differentiated cells, the receptor substrate (LB)-conjugated bioactive thermogel provides compatible microenvironments for the differentiated cells, and thus gives pronounced positive results on the differentiation of the stem cells into target cells during three-dimensional culture, compared with a passive thermogel.

摘要

为研究靶细胞的受体底物对干细胞分化的影响,合成了乳糖酸共轭聚[(聚丙二醇)-(聚乙二醇)-(聚丙二醇)]-聚(L-丙氨酸)(LB-PLX-PA),然后构建了由LB-PLX-PA和PLX-PA按0/100(LB-0)、5/95(LB-5)和20/80(LB-20)比例组成的热凝胶体系,作为一种可注射的三维支架用于扁桃体来源的间充质干细胞(TMSCs)向肝细胞分化。由于体系在37°C时发生热诱导的溶胶-凝胶转变(在此过程中TMSCs被包埋于凝胶中),LB-0、LB-5和LB-20在37°C(凝胶态)时的模量增加到500-800 Pa。基于分化细胞的生物标志物表达和肝脏生物功能,受体底物(LB)共轭的生物活性热凝胶为分化细胞提供了相容的微环境,因此与被动热凝胶相比,在三维培养过程中干细胞向靶细胞的分化方面给出了显著的阳性结果。

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