Genetic Background and Kinetics Define Wound Bed Extracellular Vesicles in a Mouse Model of Cutaneous Injury.
Genetic Background and Kinetics Define Wound Bed Extracellular Vesicles in a Mouse Model of Cutaneous Injury.
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遗传背景和动力学在小鼠皮肤损伤模型中定义伤口床细胞外小泡。
DOI：
10.3390/ijms22073551
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发表时间：
2021-03-29
影响因子：
5.6
通讯作者：
Eliceiri BP
中科院分区：
文献类型：
--
作者：
Qian J;Park DJ;Perrott S;Patel P;Eliceiri BP
细胞外囊泡（EV）在炎症中介导细胞间信号传导并影响伤口愈合的动力学方面具有重要作用，然而，对调节这些反应的机制的理解仍然有限。因此，我们专注于使用皮肤损伤模型来研究EV在伤口愈合的炎症阶段的生物学。为此，使用无菌皮下聚乙烯醇（PVA）海绵的异物反应非常适合免疫细胞和EV的平行分析，而无需组织解离，这将引入额外的变量。我们之前已经使用这个模型来识别EV生物发生的介质，确定如何控制EV的制造会影响其有效载荷和生物活性。这些在正常小鼠中的研究使我们考虑了免疫缺陷和肥胖等疾病如何影响免疫细胞和EV在该模型中使用遗传定义的突变小鼠的特征。由于EV在生物液体中本质上是异质性的，因此我们将研究重点放在一种新技术上，即囊泡流式细胞术（vFC），以量化小鼠模型中EV的变化。在这里，我们表明骨髓源性免疫细胞和EV表达与PVA海绵植入物中的抗原呈递相关的蛋白质，这些蛋白质在野生型免疫缺陷（NOD scid）小鼠与糖尿病（Leprdb）小鼠中具有不同的特征。总之，这些结果为免疫细胞和EV的并行分析奠定了基础，这些技术开始解决伤口床中细胞间通讯的异质性。
Extracellular vesicles (EVs) have an important role in mediating intercellular signaling in inflammation and affect the kinetics of wound healing, however, an understanding of the mechanisms regulating these responses remains limited. Therefore, we have focused on the use of cutaneous injury models in which to study the biology of EVs on the inflammatory phase of wound healing. For this, the foreign body response using sterile subcutaneous polyvinylalcohol (PVA) sponges is ideally suited for the parallel analysis of immune cells and EVs without the need for tissue dissociation, which would introduce additional variables. We have previously used this model to identify mediators of EV biogenesis, establishing that control of how EVs are made affects their payload and biological activity. These studies in normal mice led us to consider how conditions such as immunodeficiency and obsesity affect the profile of immune cells and EVs in this model using genetically defined mutant mice. Since EVs are intrinsically heterogenous in biological fluids, we have focused our studies on a novel technology, vesicle flow cytometry (vFC) to quantify changes in EVs in mouse models. Here, we show that myeloid-derived immune cells and EVs express proteins relevant in antigen presentation in PVA sponge implants that have distinct profiles in wildtype, immune-deficient (NOD scid) vs. diabetic (Leprdb) mice. Together, these results establish a foundation for the parallel analysis of both immune cells and EVs with technologies that begin to address the heterogeneity of intercellular communication in the wound bed.
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影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
影响因子：
4.6
作者：
Ferreira, Andrea da Fonseca;Gomes, Dawidson Assis
通讯作者：
Gomes, Dawidson Assis
影响因子：
16
作者：
Patel DB;Santoro M;Born LJ;Fisher JP;Jay SM
通讯作者：
Jay SM
影响因子：
4.4
作者：
Elsner, Leslie;Muppala, Vijayakumar;Dressel, Ralf
通讯作者：
Dressel, Ralf
影响因子：
2.2
作者：
Gibran, NS;Jang, YC;Olerud, JE
通讯作者：
Olerud, JE