Redirecting differentiation of mammary progenitor cells by 3D bioprinted sweat gland microenvironment
Redirecting differentiation of mammary progenitor cells by 3D bioprinted sweat gland microenvironment
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通过3D生物打印汗腺微环境重定向乳腺祖细胞的分化
DOI：
10.1186/s41038-019-0167-y
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发表时间：
2019-09-23
期刊：
影响因子：
5.3
通讯作者：
Fu，Xiaobing
中科院分区：
文献类型：
--
作者：
Wang，Rui;Wang，Yihui;Fu，Xiaobing
背景乳腺祖细胞（MPCs）维持其生殖能力，其特定的微环境对这些细胞起决定性的控制作用。微生物体因其可及性和持续的生后发育变化，为研究工程微环境影响提供了一种理想的工具。我们的研究的目的是探索的工程化的汗腺（SG）微环境中重新编程成功能SG cells.MethodsWe的MPC的关键作用，利用了一个三维（3D）SG微环境组成的明胶-藻酸盐水凝胶和组件从小鼠SG细胞外基质（SG-ECM）蛋白重新路由的MPC的分化，研究这个微环境的功能。将MPC封装到人工SG微环境中，并打印成3D细胞负载构建体。结果与对照组相比，免疫荧光和基因表达检测显示，生物打印3D-SG微环境包封的MPCs可显著表达小鼠SG的功能标志物钠/钾通道蛋白ATP 1a 1，并倾向于表达腔上皮细胞的特异性标志物角蛋白8。当Shh通路被抑制时，在相同的诱导环境下，MPCs中SG相关蛋白的表达显着降低。ConclusionsOur证据证明了分化的小鼠MPCs通过体外工程SG微环境再生SG细胞的能力，Shh通路被发现与分化的变化相关。这些结果提供了通过MPC再生受损SG以及工程微环境在重编程细胞命运中的作用的见解。
BackgroundMammary progenitor cells (MPCs) maintain their reproductive potency through life, and their specific microenvironments exert a deterministic control over these cells. MPCs provides one kind of ideal tools for studying engineered microenvironmental influence because of its accessibility and continually undergoes postnatal developmental changes. The aim of our study is to explore the critical role of the engineered sweat gland (SG) microenvironment in reprogramming MPCs into functional SG cells.MethodsWe have utilized a three-dimensional (3D) SG microenvironment composed of gelatin-alginate hydrogels and components from mouse SG extracellular matrix (SG-ECM) proteins to reroute the differentiation of MPCs to study the functions of this microenvironment. MPCs were encapsulated into the artificial SG microenvironment and were printed into a 3D cell-laden construct. The expression of specific markers at the protein and gene levels was detected after cultured 14 days.ResultsCompared with the control group, immunofluorescence and gene expression assay demonstrated that MPCs encapsulated in the bioprinted 3D-SG microenvironment could significantly express the functional marker of mouse SG, sodium/potassium channel protein ATP1a1, and tend to express the specific marker of luminal epithelial cells, keratin-8. When the Shh pathway is inhibited, the expression of SG-associated proteins in MPCs under the same induction environment is significantly reduced.ConclusionsOur evidence proved the ability of differentiated mouse MPCs to regenerate SG cells by engineered SG microenvironment in vitro and Shh pathway was found to be correlated with the changes in the differentiation. These results provide insights into regeneration of damaged SG by MPCs and the role of the engineered microenvironment in reprogramming cell fate.