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Modulation of biological activities in adipose derived stem cells by histone deacetylation
Sallam Abdallah1, Mouna Tabebi1,2, Sawsan Qanadilo3
1The Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Abstract:
Difficult-to-heal wounds management accounts for about 4% of healthcare costs, highlighting the need for innovative solutions. Extracellular signals drive cell proliferation during tissue regeneration, while epigenetic mechanisms regulate stem cell homeostasis, differentiation, and skin repair. Exploring epigenetic regulation in adipose-derived stem cells (ADSCs) holds promise for improving skin injury treatments. We investigated the effects of histone deacetylase inhibitor (SAHA) on ADSCs to better understand its cellular and molecular impacts. ADSCs were treated with SAHA for 72 h, showing no change in cell viability at the studied concentrations. However, the expression of histone deacetylase decreased at 1000 nM, while the cell proliferation marker Ki-67 increased after SAHA treatment, as confirmed by immunofluorescence. CCND1 gene expression increased, whereas protein expression of the proliferating cell nuclear antigen (PCNA) decreased. Cell cycle analysis showed an increase in G2 phase in SAHA-treated cells. Microarray analysis revealed 74 upregulated and 40 downregulated differentially expressed genes, including upregulation of P53 targets, CDKN1A and MDM2. Proteomic analysis identified 631 upregulated and 823 downregulated proteins compared to the vehicle. Pathway enrichment analysis showed cell cycle, ATP-dependent chromatin remodeling and DNA processes were among the affected pathways. This study suggests SAHA modulates ADSCs' biological processes, highlighting its potential for skin regeneration.
Insights
The histone deacetylase inhibitor SAHA enhances adipose-derived stem cells (ADSCs) proliferation and modulates gene expression, offering potential for improved skin regeneration therapies.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Epigenetics
Background:
- Difficult-to-heal wounds represent a significant healthcare cost, necessitating novel therapeutic strategies.
- Epigenetic mechanisms are crucial for stem cell function and tissue repair, particularly in skin regeneration.
- Adipose-derived stem cells (ADSCs) are promising for regenerative medicine due to their accessibility and multipotent nature.
Purpose of the Study:
- To investigate the effects of the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), on ADSCs.
- To elucidate the cellular and molecular mechanisms underlying SAHA's impact on ADSCs for potential skin regeneration applications.
Main Methods:
- ADSCs were treated with varying concentrations of SAHA.
- Cell viability, proliferation (Ki-67), histone deacetylase expression, CCND1 gene, and proliferating cell nuclear antigen (PCNA) protein levels were assessed.
- Cell cycle analysis, microarray, and proteomic analyses were performed to evaluate global molecular changes.
- Immunofluorescence and pathway enrichment analyses were utilized to confirm findings.
Main Results:
- SAHA treatment did not affect ADSC viability but decreased histone deacetylase expression at 1000 nM.
- SAHA increased Ki-67 expression and CCND1 gene expression, while PCNA protein levels decreased.
- Cell cycle analysis revealed an increased G2 phase population in SAHA-treated cells.
- Microarray and proteomic analyses identified significant alterations in gene and protein expression, including upregulation of p53 targets and pathways related to cell cycle and chromatin remodeling.
Conclusions:
- SAHA modulates key biological processes in ADSCs, including cell cycle progression and chromatin remodeling.
- The observed effects suggest SAHA's potential as a therapeutic agent to enhance ADSC function for skin regeneration.
- Further research into SAHA's epigenetic modulation of ADSCs could lead to innovative treatments for challenging wounds.
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