Mesenchymal Stem Cell Extracellular Vesicles from Tissue-Mimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets.
Mesenchymal Stem Cell Extracellular Vesicles from Tissue-Mimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets.
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DOI：
10.1007/s13770-023-00565-6
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发表时间：
2023-10
影响因子：
3.6
通讯作者：
Mellott, Adam J.
中科院分区：
文献类型：
--
作者：
Hodge, Jacob G.;Robinson, Jennifer L.;Mellott, Adam J.
脂肪间充质干细胞（ASC）的分泌组提供了一种独特的方法来理解和治疗伤口，包括角质形成细胞协调的表皮再生的关键过程。然而，2D培养技术极大地改变了ASC的分泌动力学，这导致了在理解哪些分泌的化合物（例如，生长因子、外来体、活性氧物质）可能驱动上皮形成。一种新型的组织模拟3D水凝胶系统被用来增强更再生的ASC表型的保留，并突出2D和3D之间的功能性分泌组差异。随后，ASC-分泌组通过分子量和细胞外囊泡（EV）的存在/不存在进行分层。然后评价ASC-分泌组级分以评估增强特定角质形成细胞活性的能力。在组织模拟系统内培养ASC使蛋白质分泌增加约50%，仅来自> 100 kDa部分。ASC-分泌组调节上皮形成功能（包括迁移、增殖、分化和形态）的能力存在于“> 100 kDa”级分内，其中3D ASC-分泌组提供最大的改善。3D ASC EV分泌增强两倍，并对表皮再生表现出剂量依赖性作用。值得注意的是，ASC-EV诱导角质形成细胞的形态学变化，使人联想到天然再生，包括分层细胞片的形成。然而，只有3D-EV促进角质形成细胞中的集体细胞片迁移和上皮向间充质样转变，而2D-EV含有抗迁移刺激。这项研究证明了培养环境对影响ASC分泌组再生能力的重要性。此外，揭示了EV在调节表皮再生中的关键作用，并讨论了其对未来临床治疗的可翻译性。在线版本包含补充材料，可通过10.1007/s13770-023-00565-6获得。
The secretome of adipose-derived mesenchymal stem cells (ASCs) offers a unique approach to understanding and treating wounds, including the critical process of epidermal regeneration orchestrated by keratinocytes. However, 2D culture techniques drastically alter the secretory dynamics of ASCs, which has led to ambiguity in understanding which secreted compounds (e.g., growth factors, exosomes, reactive oxygen species) may be driving epithelialization. A novel tissue-mimetic 3D hydrogel system was utilized to enhance the retainment of a more regenerative ASC phenotype and highlight the functional secretome differences between 2D and 3D. Subsequently, the ASC-secretome was stratified by molecular weight and the presence/absence of extracellular vesicles (EVs). The ASC-secretome fractions were then evaluated to assess for the capacity to augment specific keratinocyte activities. Culture of ASCs within the tissue-mimetic system enhanced protein secretion ~ 50%, exclusively coming from the > 100 kDa fraction. The ASC-secretome ability to modulate epithelialization functions, including migration, proliferation, differentiation, and morphology, resided within the “> 100 kDa” fraction, with the 3D ASC-secretome providing the greatest improvement. 3D ASC EV secretion was enhanced two-fold and exhibited dose-dependent effects on epidermal regeneration. Notably, ASC-EVs induced morphological changes in keratinocytes reminiscent of native regeneration, including formation of stratified cell sheets. However, only 3D-EVs promoted collective cell sheet migration and an epithelial-to-mesenchymal-like transition in keratinocytes, whereas 2D-EVs contained an anti-migratory stimulus. This study demonstrates how critical the culture environment is on influencing ASC-secretome regenerative capabilities. Additionally, the critical role of EVs in modulating epidermal regeneration is revealed and their translatability for future clinical therapies is discussed. The online version contains supplementary material available at 10.1007/s13770-023-00565-6.
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影响因子：
5.6
作者：
Baldari S;Di Rocco G;Piccoli M;Pozzobon M;Muraca M;Toietta G
通讯作者：
Toietta G
DOI：
10.1002/dvdy.24561
发表时间：
2018-03
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Haensel D;Dai X
通讯作者：
Dai X
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：
Gerardo, Heloisa;Lima, Ana;Graos, Mario
通讯作者：
Graos, Mario
影响因子：
2.7
作者：
Baraniak PR;McDevitt TC
通讯作者：
McDevitt TC