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聚(3-羟基丁酸-co-3-羟基戊酸酯)被认为是一种人工细胞外基质,可促进人诱导多能干细胞的成骨分化。

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) improved osteogenic differentiation of the human induced pluripotent stem cells while considered as an artificial extracellular matrix.

机构信息

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Dietary supplements and probiotic research center, Alborz University of Medical Sciences, Karaj, Iran.

出版信息

J Cell Physiol. 2019 Jul;234(7):11537-11544. doi: 10.1002/jcp.27807. Epub 2018 Nov 27.

DOI:10.1002/jcp.27807
PMID:30478907
Abstract

Cocell polymers can be the best implants for replacing bone defects in patients. The pluripotent stem cells produced from the patient and the nanofibrous polymeric scaffold that can be completely degraded in the body and its produced monomers could be also usable are the best options for this implant. In this study, electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers were fabricated and characterized and then osteogenic differentiation of the human-induced pluripotent stem cells (iPSCs) was investigated while cultured on PHBV scaffold. MTT results showed that cultured iPSCs on PHBV proliferation were increased compared to those cultured on tissue culture polystyrene (TCPS) as the control. Alkaline phosphatase (ALP) activity and calcium content were also significantly increased in iPSCs cultured on PHBV compared to the cultured on TCPS under osteogenic medium. Gene expression evaluation demonstrated that Runx2, collagen type I, ALP, osteonectin, and osteocalcin were upregulated in iPSCs cultured on PHBV scaffold in comparison with those cultured on TCPS for 2 weeks. Western blot analysis have shown that osteocalcin and osteopontin expression as two major osteogenic markers were increased in iPSCs cultured on PHBV scaffold. According to the results, nanofiber-based PHBV has a promising potential to increase osteogenic differentiation of the stem cells and iPSCs-PHBV as a cell-co-polymer construct demonstrated that has a great efficiency for use as a bone tissue engineered bioimplant.

摘要

壳聚糖聚合物可以成为患者骨缺损替代物的最佳植入物。从患者中产生的多能干细胞和可在体内完全降解的纳米纤维聚合物支架及其产生的单体也是这种植入物的最佳选择。在这项研究中,制备并表征了电纺聚(3-羟基丁酸酯-co-3-羟基戊酸酯)(PHBV)纳米纤维,然后研究了人诱导多能干细胞(iPSCs)在 PHBV 支架上培养时的成骨分化。MTT 结果表明,与作为对照的组织培养聚苯乙烯(TCPS)相比,在 PHBV 支架上培养的 iPSCs 增殖增加。与在成骨培养基中在 TCPS 上培养相比,在 PHBV 上培养的 iPSCs 的碱性磷酸酶(ALP)活性和钙含量也显著增加。基因表达评估表明,与在 TCPS 上培养相比,在 PHBV 支架上培养的 iPSCs 中 Runx2、I 型胶原、ALP、骨粘连蛋白和骨钙素的表达上调。Western blot 分析表明,在 PHBV 支架上培养的 iPSCs 中两种主要成骨标志物骨钙素和骨桥蛋白的表达增加。根据这些结果,基于纳米纤维的 PHBV 具有增加干细胞和成骨分化的潜力,iPSCs-PHBV 作为一种细胞共聚物构建体,证明其作为骨组织工程生物植入物的效率很高。

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