Dataset Information

Hydrogel-Encapsulated Primed Mesenchymal Stem Cells Enhance Regeneration and Immune Modulation in Full-Thickness Burn Wounds

ABSTRACT: Severe burn injuries pose significant clinical challenges, with high risks of infection, excessive inflammation, and impaired wound healing. Mesenchymal stem cells (MSCs) have shown regenerative and antimicrobial potential; however, their therapeutic efficacy is constrained by poor survival and engraftment. Here, we demonstrate that priming MSCs with insulin-secreting cells (ISCs) and encapsulating them in hydrogels (HEMI) enhances their regenerative function, leading to accelerated healing of full-thickness burns in a porcine model. Wounds treated with HEMIs achieved 80% closure within five weeks, compared to 50% in MSC-only and 0% in standard-of-care controls. Histological analysis revealed complete epidermal and dermal regeneration with minimal fibrosis in HEMI-treated wounds. Single-cell RNA sequencing (scRNA-seq) and differentially abundant sequencing (DA-seq) analysis identified distinct MSC subpopulations transitioning from a proliferative to a tissue-remodeling phenotype, with insulin priming promoting pathways involved in extracellular matrix (ECM) stabilization, immune modulation, and oxidative stress resistance. Our findings suggest that insulin priming enhances MSC-mediated tissue repair via paracrine mechanisms, providing a clinically translatable strategy for improving burn treatment and regenerative medicine applications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307777 | GEO | 2026/06/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Non-healing wounds cause profound suffering of patients and a huge economic burden on society. Current research attempts to refine MSC-based therapies for this type of difficult-to-treat wounds. We earlier reported that injection of S100A8/A9 primed MSCs into the wound edge in mice accelerates wound healing compared to non-primed MSCs. We here describe a protective response of differentially expressed isoforms of genes, proteins and their potential role in the reported beneficial effects of S100A8/A9 primed MSCs on tissue repair. Methods: Adipose‐derived MSCs were characterized for specific cell surface markers using flow cytometry and assessed for their ability to differentiate into different lineages. To further investigate the mechanisms underlying the beneficial effects of S100A8/A9 primed MSCs, we employed a multi‐omics strategy that combined transcriptome, secretome, and proteome analyses. Global translational activity and a potential metabolic shift were examined using fluorescent labeling alongside seahorse‐based metabolic assays. Additionally, in silico analysis was conducted to assess the presence of the DRACH motif in mRNAs encoding these proteins, thereby evaluating their potential for cap-independent, m6A‐mediated translation. Results: Enhanced protein translation was observed in MSCs primed with S100A8/A9. Priming significantly increased the levels of the cap-independent translation initiation factor EIF3I, while reducing the cap-dependent factor EIF4A1, suggesting a shift in the mode of translation. In addition, the secretome of S100A8/A9-primed MSCs exhibited upregulation of cystatin C, a tissue protective protease inhibitor, and angiopoietin-1, an inducer of angiogenesis. Furthermore, various collagens, which serve as MSC niche-protecting proteins, were expressed at higher levels in the S100A8/A9 primed MSCs. Notably, the mRNAs corresponding to these factors contained DRACH motifs. Conclusion: We uncovered a protective response in S100A8/A9 primed MSCs that alters translation processes and increases the secretion of protective proteins, whose functions warrant further exploration. In the long term, S100A8/A9 priming holds promise for developing more effective MSC‐based therapies to enhance wound healing.

Project description:Age-related bone degeneration is driven by structural deterioration, chronic inflammation, and impaired regenerative capacity, leading to an increased incidence of osteoarticular disorders. Mesenchymal stromal/stem cells (MSCs) have emerged as promising therapeutic candidates due to their immunomodulatory and regenerative properties, mediated largely through their secretome and extracellular vesicles (EVs). However, the therapeutic efficacy of MSC-derived products depends on both the cell source and the conditioning stimuli to which MSCs are exposed. In this study, we performed a comparative proteomic and exosomal microRNA (miRNA) profiling of secretomes derived from placenta-derived MSCs (PSCs) and adipose-derived MSCs (ASCs), and assessed the impact of priming strategies, including hypoxia, interferon-gamma (IFNγ), and interleukin-1 beta (IL1β), on paracrine properties of these cells. Proteomic analysis identified over 7,000 proteins, with PSC secretome enriched in pathways related to osteogenesis, chondrogenesis, extracellular matrix organization, angiogenesis, and immune regulation, whereas ASC secretome displayed limited enrichment in these processes. Functional scoring highlighted IL1β priming as the most effective strategy to enhance osteochondral and immunomodulatory protein signatures in PSCs. Differently, IFNγ priming selectively expanded the repertoire of exosomal miRNAs, with enrichment in signaling networks including Wnt/β-catenin, TGF-β, NF-κB, and T cell receptor pathways, underscoring its role in fine-tuning immune and regenerative functions. Together, these findings reveal that PSCs secrete a broader and more functionally relevant spectrum of bioactive molecules for osteoarticular applications compared with ASCs. Moreover, distinct priming strategies can differentially modulate their paracrine outputs. IL1β primarily enhances protein-driven regenerative and immunomodulatory activity, whereas IFNγ promotes a functionally enriched exosomal miRNA cargo. These results support PSC-derived secretomes as versatile candidates for next-generation, cell-free therapies in osteoarticular disease.

Dataset Information

Hydrogel-Encapsulated Primed Mesenchymal Stem Cells Enhance Regeneration and Immune Modulation in Full-Thickness Burn Wounds

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets