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在基于 3D 水凝胶的培养系统中,硅纳米粒子的表面化学性质极大地影响间充质干细胞的命运。

The fate of mesenchymal stem cells is greatly influenced by the surface chemistry of silica nanoparticles in 3D hydrogel-based culture systems.

机构信息

Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), P.O. Box: 14965/161, Tehran, Iran; Department of Regenerative Biomaterials, Radboud University Medical Center, Philips van Leydenlaan 25, Nijmegen, 6525 EX, the Netherlands.

Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), P.O. Box: 14965/161, Tehran, Iran.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Jan;106:110259. doi: 10.1016/j.msec.2019.110259. Epub 2019 Oct 14.

DOI:10.1016/j.msec.2019.110259
PMID:31753381
Abstract

Polymeric hydrogel-based 3D scaffolds are well-known structures, being used for cultivation and differentiation of stem cells. However, scalable systems that provide a native-like microenvironment with suitable biological and physical properties are still needed. Incorporation of nanomaterials into the polymeric systems is expected to influence the physical properties of the structure but also the stem cells fate. Here, alginate/gelatin hydrogel beads incorporated with mesoporous silica nanoparticles (MSNs) (average diameter 80.9 ± 10 nm) and various surface chemistries were prepared. Human adipose-derived mesenchymal stem cells (hASCs) were subsequently encapsulated into the alginate/gelatin/silica hydrogels. Incorporation of amine- and carboxyl-functionalized MSNs (A-MSNs and C-MSNs) significantly enhances the stability of the hydrogel beads. In addition, the expression levels of Nanog and OCT4 imply that the incorporation of A-MSNs into the alginate/gelatin beads significantly improves the proliferation and the stemness of encapsulated hASCs. Importantly, our findings show that the presence of A-MSNs slightly suppresses in vivo inflammation. In contrast, the results of marker gene expression analyses indicate that cultivation of hASCs in alginate beads incorporated with C-MSNs (10% w/w) leads to a heterogeneously differentiated population of the cells, i.e., osteocytes, chondrocytes, and adipocytes, which is not appropriate for both cell culture and differentiation applications.

摘要

基于聚合水凝胶的 3D 支架是众所周知的结构,用于干细胞的培养和分化。然而,仍然需要可扩展的系统,为干细胞提供类似天然的微环境,具有合适的生物学和物理特性。将纳米材料纳入聚合物系统有望影响结构的物理性质,但也会影响干细胞的命运。在这里,制备了包封有介孔硅纳米粒子(MSNs)(平均直径 80.9±10nm)和各种表面化学性质的藻酸盐/明胶水凝胶珠。随后将人脂肪间充质干细胞(hASCs)包封到藻酸盐/明胶/硅水凝胶中。胺功能化和羧基功能化的 MSNs(A-MSNs 和 C-MSNs)的掺入显著提高了水凝胶珠的稳定性。此外,Nanog 和 OCT4 的表达水平表明,A-MSNs 的掺入到藻酸盐/明胶珠中显著提高了包封的 hASCs 的增殖和干性。重要的是,我们的研究结果表明,A-MSNs 的存在略微抑制了体内炎症。相比之下,标记基因表达分析的结果表明,在含有 10%w/w 的 C-MSNs 的藻酸盐珠中培养 hASCs 会导致细胞异质分化,即成骨细胞、软骨细胞和脂肪细胞,这不利于细胞培养和分化应用。

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