RISS 검색 - 국내학술지논문 상세보기

다국어 초록 (Multilingual Abstract)

BACKGROUND 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.
METHODS 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.
RESULTS 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.
CONCLUSION 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.

번역하기

참고문헌 (Reference)

1 Shaw TJ, "Wound repair at a glance" 122 : 3209-3213, 2009

2 Eming SA, "Wound repair and regeneration : mechanisms, signaling, and translation" 6 : 265sr266-, 2014

3 Safferling K, "Wound healing revised : a novel reepithelialization mechanism revealed by in vitro and in silico models" 203 : 691-709, 2013

4 Kim WS, "Wound healing effect of adipose-derived stem cells : a critical role of secretory factors on human dermal fibroblasts" 48 : 15-24, 2007

5 Juliar BA, "Viscoelastic characterization of diabetic and non-diabetic human adipose tissue" 57 : 15-26, 2020

6 Dunn MG, "Viscoelastic behavior of human connective tissues : relative contribution of viscous and elastic components" 12 : 59-70, 1983

7 Cheng F, "Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-beta-Slug signaling" 113 : E4320-E4327, 2016

8 Ge Q, "VEGF secreted by mesenchymal stem cells mediates the differentiation of endothelial progenitor cells into endothelial cells via paracrine mechanisms" 17 : 1667-1675, 2018

9 Hodge JG, "Tissue-mimetic culture enhances mesenchymal stem cell secretome capacity to improve regenerative activity of keratinocytes and fibroblasts in vitro" 31 : 367-, 2023

10 Chaicharoenaudomrung N, "Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling" 11 : 1065-1083, 2019