Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway
Abstract
Introduction Adipose tissue-derived stem cells (ADSCs) have been shown to enhance wound healing via their paracrine function. Exosomes, as one of the most important paracrine factors, play an essential role in this process. However, the concrete mechanisms that underlie this effect are poorly understood. In this study, we aim to explore the potential roles and molecular mechanisms of exosomes derived from ADSCs in cutaneous wound healing.Methods Normal human skin fibroblasts and ADSCs were isolated from patient skin and adipose tissues. ADSCs were characterized by using flow cytometric analysis and adipogenic and osteogenic differentiation assays. Exosomes were purified from human ADSCs by differential ultracentrifugation and identified by electron microscopy, nanoparticle tracking, fluorescence confocal microscopy and western blotting. Fibroblasts were treated with different concentrations of exosomes, and the synthesis of collagen was analyzed by western blotting; the levels of growth factors were analyzed by real-time quantitative PCR (RT-PCR) and ELISA; and the proliferation and migration abilities of fibroblasts were analyzed by real-time cell analysis, CCK-8 assays and scratch assays. A mouse model with a full-thickness incision wound was used to evaluate the effect of ADSC-derived exosomes on wound healing. The level of p-Akt/Akt was analyzed by western blotting. Ly294002, a phosphatidylinositol 3-kinases (PI3K) inhibitor, was used to identify the underlying mechanisms by which ADSC-derived exosomes promote wound healing.Results ADSC-derived exosomes were taken up by the fibroblasts, which showed significant, dose-dependent increases in cell proliferation and migration compared to the behavior of cells without exosome treatment. More importantly, both the mRNA and protein levels of type I collagen (Col 1), type III collagen (Col 3), MMP1, bFGF, and TGF-β1 were increased in fibroblasts after stimulation with exosomes. Furthermore, exosomes significantly accelerated wound healing in vivo and increased the level of p-Akt/Akt in vitro. However, Ly294002 alleviated these exosome-induced changes, suggesting that exosomes from ADSCs could promote and optimize collagen deposition in vitro and in vivo and further promote wound healing via the PI3K/Akt signaling pathway.Conclusions This study demonstrates that ADSC-derived exosomes can promote fibroblast proliferation and migration and optimize collagen deposition via the PI3K/Akt signaling pathway to further accelerate wound healing. Our results suggest that ADSCs likely facilitate wound healing via the release of exosomes, and the PI3K/Akt pathway may play a role in this process. Our data also suggest that the clinical application of ADSC-derived exosomes may shed new light on the use of cell-free therapy to accelerate full-thickness skin wound healing and attenuate scar formation.
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Adipose tissue-derived stem cell exosomes can accelerate collagen synthesis and redeposition through regulating PI3K/Akt pathway, reducing healing time and scarring in mouse models.
“Similarly, Zhang et al. found that exosomes from adipose tissue-derived stem cells can accelerate collagen synthesis and redeposition through regulating PI3K/Akt pathway. This function helps in full-thickness skin wounds, ultimately reducing healing time and scarring in mouse models [103].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [103]
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- Authors
- Zhang, W., Bai, X., Zhao, B., Li, Y., Zhang, Y., Li, Z., Wang, X., Luo, L., Han, F., Zhang, J., Han, S., Cai, W., Su, L., Tao, K., Shi, J., & Hu, D.
- Affiliations
- Xi'an Medical University (CN)
- Xijing Hospital (CN)
- Corresponding author
- Hu, Dahai
- ORCID
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 370
- Issue
- 2
- Pages
- 333-342
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2810276296
- Cited by
- 361
- References
- 37
- Citations by year
- 2026: 20 · 2025: 45 · 2024: 61 · 2023: 52 · 2022: 66 · 2021: 60 · 2020: 39 · 2019: 15 · 2018: 2
- FWCI
- 24.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81372069, 81772071)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- adipose-derived stem cells, exosomes, cell-free therapy, wound healing, PI3K/Akt signaling, dermal fibroblasts, collagen deposition, fibroblast proliferation and migration, paracrine signaling, TGF-β1, basic fibroblast growth factor, MMP-1, PI3K inhibitors
- MeSH terms
- Adipose Tissue, Adolescent, Adult, Animals, Cell Differentiation, Cell Movement, Child, Child, Preschool, Fibroblasts, Humans, Osteogenesis, Skin, Stem Cells, Wound Healing, Phosphatidylinositol 3-Kinases, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice, Exosomes, Young Adult
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