Regulation of mesenchymal stem cell osteogenic potential via microfluidic manipulation of microcarrier surface curvature

微载波 间充质干细胞 PLGA公司 细胞生物学 化学 拉明 干细胞 微流控 机械生物学 细胞分化 细胞 生物医学工程 纳米技术 材料科学 生物 体外 生物化学 核心 医学 基因
作者
Ziyang Jin,Yishu Zhai,Yi Zhou,Pan Guo,Miaomiao Chai,Wen‐Song Tan,Yan Zhou,Lian Cen
出处
期刊:Chemical Engineering Journal [Elsevier BV]
卷期号:448: 137739-137739 被引量:21
标识
DOI:10.1016/j.cej.2022.137739
摘要

Microsphere-carriers have gained great interests as three-dimensional substrates for cultivation/expansion of tissue cells, required by cell-based therapy. However, how the microsphere curvature affects the cell proliferation/differentiation as well as the underlying signaling pathway of stem cells, and how to consequently regulate those cellular functionalities via manipulating microcarrier surface curvature, still remain to be explored. The current study was thus designed to develop a microfluidic manipulation technology to precisely control poly (lactic-co-glycolic) acid (PLGA) microsphere surface curvature, and subsequently to investigate the cellular responses and responding pathways of rat bone mesenchymal stem cells (BMSCs) cultured on these microspheres of predetermined curvature. A microfluidic device was developed to produce mono-distributed PLGA microspheres of diameters ranging from 52 µm to 250 µm, corresponding to curvatures (κ) from 1/26 µm−1 to 1/125 µm−1. BMSCs attachment and proliferation was evaluated on them and the one of κ = 1/82.5 µm−1 was shown to provide the most suitable microenvironment for cells to grow and undergo osteogenic differentiation. It was even found that F-actin cytoskeletal organization, nuclear distortion and expression of Lamin A were significantly enhanced by cells on the microcarriers of κ = 1/82.5 µm−1. Furthermore, a long non-coding RNA named lnc-LMNA, was found in this study to be the key factor associated with Lamin A to regulate osteogenic differentiation of BMSCs on spherical substrates. The current study thus provides a smart manipulation technology via microfluidic-manufacturing microcarriers to regulate cell functionalities, thereby enhancing desired therapeutic outcomes of cell-based regeneration or repair.
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