Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation.
Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation.
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DOI：
10.3389/fbioe.2018.00108
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发表时间：
2018
影响因子：
5.7
通讯作者：
Vrana NE
中科院分区：
文献类型：
--
作者：
Barthes J;Dollinger C;Muller CB;Liivas U;Dupret-Bories A;Knopf-Marques H;Vrana NE
软组织的功能与它们与身体的其他系统，如循环、神经系统和免疫系统的联系错综复杂。组织中驻留巨噬细胞的存在提供了一种控制组织动态平衡的手段，也提供了一种对物理/生物伤害和组织损伤做出反应的方法。因此，在工程组织中掺入表型控制的驻留巨噬细胞可以提高其作为模型组织的保真度，并提高其整合率，促进再生医学应用中的炎症消退。在此，我们展示了在含有成纤维细胞和/或内皮细胞的三维(3-D)明胶水凝胶中免疫辅助工程化软组织重塑过程的两种潜在方法：(I)在巨噬细胞存在的情况下添加白细胞介素4(IL-4)；(Ii)通过幼稚的单核细胞或分化的巨噬细胞进行三次培养。IL-4的存在对成纤维细胞具有增殖作用，在分化的巨噬细胞存在的情况下，通过上调激活素、白介素1受体拮抗剂(IL-1RA)、肿瘤坏死因子α(TN-α)和白介素1β(IL-1β)的表达，显著促进细胞的增殖和细胞因子的分泌，创造更具刺激性的微环境。在内皮细胞/巨噬细胞共培养体系中加入IL-4改善了萌芽样结构的组织，在分化的巨噬细胞存在的情况下，促进了第1天的增殖，并在最早阶段上调了IL-6和IL-1RA的表达，为血管生成创造了有利的微环境。在三种培养条件下，单核细胞或巨噬细胞的存在导致水凝胶高度重塑，形成致密的组织样结构。分化的巨噬细胞的存在对血管生成的分泌微环境有促进作用，如IL-6和IL-8，而不需要任何额外的细胞因子补充。成纤维细胞和内皮细胞的存在对血管生成素的分泌也有显著的影响。我们的结果表明，巨噬细胞在常驻巨噬细胞功能中的掺入及其表型控制对三维多细胞类型水凝胶的成熟和细胞因子微环境有显著影响，这可以被用于更好地整合植入系统和具有免疫成分的更具生理相关性的体外组织模型。
The function of soft tissues is intricately linked to their connections with the other systems of the body such as circulation, nervous system, and immune system. The presence of resident macrophages in tissues provides a means to control tissue homeostasis and also a way to react to the physical/biological insults and tissue damage. Thus, incorporation of resident macrophage like phenotype-controlled macrophages in engineered tissues can improve their fidelity as model tissues and also improve their rate of integration and facilitate the resolution of inflammation for regenerative medicine applications. Herein, we demonstrate two potential ways to immunoassist the remodeling process of engineered soft tissues in three-dimensional (3-D) gelatin based hydrogels containing fibroblasts and/or endothelial cells: (i) with supplementation of interleukin-4 (IL-4) in the presence of macrophages and (ii) in tri-culture via naive monocytes or differentiated macrophages. The presence of IL-4 had a proliferative effect on fibroblasts, with a significant boosting effect on proliferation and cytokine secretion in the presence of differentiated macrophages with an upregulation of activin, interleukin-1 receptor antagonist (IL-1RA), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), creating a more stimulating microenvironment. The addition of IL-4 in endothelial cell/macrophage co-culture configuration improved the organization of the sprout-like structures, with a boost in proliferation at day 1 and with an upregulation of IL-6 and IL-1RA at the earliest stage in the presence of differentiated macrophages creating a favorable microenvironment for angiogenesis. In tri-culture conditions, the presence of monocytes or macrophages resulted in a denser tissue-like structure with highly remodeled hydrogels. The presence of differentiated macrophages had a boosting effect on the angiogenic secretory microenvironment, such as IL-6 and IL-8, without any additional cytokine supplementation. The presence of fibroblasts in combination with endothelial cells also had a significant effect on the secretion of angiopoietin. Our results demonstrate that incorporation of macrophages in a resident macrophage function and their phenotype control have significant effects on the maturation and cytokine microenvironment of 3-D multiple cell type-laden hydrogels, which can be harnessed for better integration of implantable systems and for more physiologically relevant in vitro tissue models with an immune component.
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DOI：
10.1083/jcb.146.4.831
发表时间：
1999-08-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Correia I;Chu D;Chou YH;Goldman RD;Matsudaira P
通讯作者：
Matsudaira P
影响因子：
14
作者：
Bigi, A;Cojazzi, G;Rubini, K
通讯作者：
Rubini, K
影响因子：
4.4
作者：
Fukushi, J;Ono, M;Kuwano, W
通讯作者：
Kuwano, W
影响因子：
1.8
作者：
Jus, Suzana;Stachel, Ines;Guebitz, Georg M.
通讯作者：
Guebitz, Georg M.
影响因子：
30.5
作者：
Dardalhon, Valerie;Awasthi, Amit;Kwon, Hyoung;Galileos, George;Gao, Wenda;Sobel, Raymond A.;Mitsdoerffer, Meike;Strom, Terry B.;Elyaman, Wassim;Ho, I-Cheng;Khoury, Samia;Oukka, Mohamed;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.