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Paracrine signalling from monocytes enables desirable extracellular matrix accumulation and temporally appropriate phenotype of vascular smooth muscle cell-like cells derived from adipose stromal cells.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2019-12-09 , DOI: 10.1016/j.actbio.2019.12.006
Xiaoqing Zhang 1 , Craig A Simmons 2 , J Paul Santerre 3
Affiliation  

In vascular tissue engineering, the ability to obtain a robust and safe vascular tissue cell source (e.g. vascular smooth muscle cells (VSMCs)) and to promote vascular tissue-specific extracellular matrix (ECM) protein production is critically important. Mature blood vessel-derived VSMCs are not practical for in vitro vascular tissue regeneration. The authors have conceived a strategy to differentiate adipose derived stromal cells (ASCs) into VSMC-like cells (ASC-VSMCs) that were similar to mature umbilical artery VSMCs at the transcriptional, protein and contraction function levels. Monocytes/macrophages are known as important regulators of the inflammation and regeneration processes within different tissue types of the body. However, our understanding of the potential interactions between specific tissue-like cells differentiated from stem/stromal cells (e.g. ASC-VSMCs) and monocytes/macrophages (cued by specific biomaterial scaffolds) is still limited. In this study, indirect and direct ASC-VSMC-monocyte co-cultures were constructed within a porous polyurethane scaffold (D-PHI) previously shown to have an immunomodulatory character. The effects of monocytes/macrophages on the cellularity (cell number detected with DNA quantification assay), ECM (glycosaminoglycan (GAG), collagen, and elastin) accumulation as well as the maintenance of contractile VSMC markers (calponin and smoothelin) of the ASC-VSMCs after a month of co-culture were investigated. It was found that monocyte paracrine signalling in D-PHI positively affected the cellularity and ECM accumulation of ASC-VSMCs in co-culture. Cause-effect relationships were also identified between the release of pro-inflammatory/anti-inflammatory factors (i.e. IL6, TGF-β1) in co-culture and the expression of contractile proteins (calponin and smoothelin) by ASC-VSMCs. This study demonstrated the importance of combining an immune cell strategy with stromal cell derived VSMCs (i.e. ASC-VSMCs) to achieve a practical vascular tissue engineering outcome. STATEMENT OF SIGNIFICANCE: Adipose stromal cell derived-vascular smooth muscle cells (ASC-VSMCs) are a promising cell source for vascular tissue engineering. Monocytes/monocyte derived macrophages can be harnessed as an immune-assisted strategy to promote vascular tissue regeneration. This study demonstrated that the co-culture of human ASC-VSMCs with monocytes significantly enhanced the cellularity and extracellular matrix (ECM) accumulation within anionic polyurethane (D-PHI) scaffolds, partially mediated by monocyte paracrine signalling mechanisms. In addition, specific VSMC contractile markers (calponin and smoothelin) were still present in ASC-VSMCs when the cells were exposed to monocytes for a month in vitro. This study corroborated the potential selection of ASC-VSMCs for in vitro engineering of vascular tissue in an immunomodulatory biomaterial scaffold (e.g. D-PHI) based co-culture system containing monocytes.

中文翻译:

来自单核细胞的旁分泌信号转导能够实现所需的细胞外基质积累和源自脂肪基质细胞的血管平滑肌细胞样细胞在时间上适当的表型。

在血管组织工程中,获得强大而安全的血管组织细胞来源(例如血管平滑肌细胞(VSMC))并促进血管组织特异性细胞外基质(ECM)蛋白产生的能力至关重要。成熟的血管源性VSMC在体外血管组织再生中并不实用。作者已经构想出一种策略,可以将脂肪来源的基质细胞(ASC)分化为VSMC样细胞(ASC-VSMC),在转录,蛋白质和收缩功能水平上它们类似于成熟的脐动脉VSMC。单核细胞/巨噬细胞被认为是体内不同组织类型内炎症和再生过程的重要调节剂。然而,我们对与干细胞/基质细胞(例如ASC-VSMC)分化的特定组织样细胞与单核细胞/巨噬细胞(由特定生物材料支架诱导)之间潜在相互作用的理解仍然有限。在这项研究中,在多孔聚氨酯支架(D-PHI)中构建了间接和直接的ASC-VSMC-单核细胞共培养物,该支架先前已显示具有免疫调节特性。单核细胞/巨噬细胞对ASC-(ASC-共培养一个月后对VSMC进行了调查。发现在共培养中,D-PHI中的单核细胞旁分泌信号转导积极影响ASC-VSMC的细胞性和ECM积累。还确定了共培养中促炎/抗炎因子(即IL6,TGF-β1)的释放与ASC-VSMCs收缩蛋白(钙皂素和柔滑素)的表达之间的因果关系。这项研究证明了将免疫细胞策略与基质细胞衍生的VSMC(即ASC-VSMC)相结合以实现实用的血管组织工程成果的重要性。意义声明:脂肪基质细胞衍生的血管平滑肌细胞(ASC-VSMC)是用于血管组织工程的有希望的细胞来源。单核细胞/单核细胞衍生的巨噬细胞可被用作促进血管组织再生的免疫辅助策略。这项研究表明,人类ASC-VSMC与单核细胞的共培养显着增强了阴离子聚氨酯(D-PHI)支架内的细胞性和细胞外基质(ECM)积累,部分由单核细胞旁分泌信号传导机制介导。另外,当细胞在体外暴露于单核细胞达一个月时,ASC-VSMC中仍存在特定的VSMC收缩标志物(钙皂素和平滑蛋白)。这项研究证实了在包含单核细胞的基于免疫调节生物材料支架(例如D-PHI)的共培养系统中,用于体外工程化血管组织的ASC-VSMC的潜在选择。部分由单核细胞旁分泌信号传导机制介导。另外,当细胞在体外暴露于单核细胞达一个月时,ASC-VSMC中仍存在特定的VSMC收缩标志物(钙皂素和平滑蛋白)。这项研究证实了在包含单核细胞的基于免疫调节生物材料支架(例如D-PHI)的共培养系统中,用于体外工程化血管组织的ASC-VSMC的潜在选择。部分由单核细胞旁分泌信号传导机制介导。此外,当细胞在体外暴露于单核细胞达一个月时,ASC-VSMC中仍存在特定的VSMC收缩标志物(钙皂素和平滑蛋白)。这项研究证实了在包含单核细胞的基于免疫调节生物材料支架(例如D-PHI)的共培养系统中,用于体外工程化血管组织的ASC-VSMC的潜在选择。
更新日期:2019-12-09
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