ArticleTissue engineering and regenerative medicine2023
Mesenchymal Stem Cell Extracellular Vesicles from Tissue-Mimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets.
Article in Tissue engineering and regenerative medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- Tuning Secretomes for Regenerative Medicine.Biology · 2026Review
- Mesenchymal Stem/Stromal Cell-Free Therapies: Challenges and Opportunities.Molecular biotechnology · 2026Review
- EXO-VNN2 derived from 3D-cultured DPSCs enhances the inflammatory response of PDLSCs and suppresses bone regeneration in periodontitis.Stem cell research & therapy · 2026Article
- Secretome as a novel regenerative strategy for atopic dermatitis: a comprehensive review.Stem cell research & therapy · 2026Review
- Extracellular vesicles from mesenchymal stem/stromal cells as emerging tools in wound healing: mechanisms and therapeutic potential.Stem cell research & therapy · 2025Review
- Comparison of 3D culture systems on mesenchymal stem cell longevity, regenerative potential, and secretome production.Regenerative medicine · 2025Article
- Three-Dimensional Bioprinting Techniques in Skin Regeneration: Current Insights and Future Perspectives.Life (Basel, Switzerland) · 2025Review
- Microenvironmental Modulation for Therapeutic Efficacy of Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Simple and Cost-Effective Generation of 3D Cell Sheets and Spheroids Using Curvature-Controlled Paraffin Wax Substrates.Nano convergence · 2024Article
- Recent Progress in Mesenchymal Stem Cell-Derived Exosomes for Skin Wound Repair.Cell biochemistry and biophysics · 2024Review
- Immunotherapy targeting the obese white adipose tissue microenvironment: Focus on non-communicable diseases.Bioactive materials · 2024Article
- Human mesenchymal stem cell secretomes: Factors affecting profiling and challenges in clinical application.Cell and tissue research · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe 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.
methodsA 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.
resultsCulture 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.
conclusionThis 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.