standardized-method-to-detect-tunneling-nanotubes-human-skin-cells

Standardized Method to Detect Tunneling Nanotubes in Human Skin Cells for Tissue Engineering Applications

Tunneling nanotubes (TNTs) are thin, actin-based intercellular conduits that enable long-range transfer of organelles and signaling cargo. Although widely ...

isolation-characterization-dental-pulp-stem-cell-derived-exosomes

Isolation and Characterization of Dental Pulp Stem Cell-Derived Exosomes Across Cell Passages

Dental pulp stem cells (DPSCs) represent an accessible and clinically relevant source of mesenchymal stem cells, and their derived exosomes have emerged ...

Hangzhou Medical College

Ningbo Stomatology Hospital

Ningbo ENT Hospital

Psoriasis is a chronic inflammatory skin disease characterized by a complex pathogenesis involving various types of cells and cytokines. Among those, the pro-inflammatory cytokine IL-23/IL-17A axis plays a crucial role in the development and rapid progression of psoriasis. Phenformin, a derivative of metformin and a member of the biguanide class of drugs, exhibits superior anti-inflammatory and anti-tumor efficacy compared to metformin. However, the potential role of phenformin in anti-psoriatic skin inflammation has not been explored.

Topical application of phenformin ameliorates the psoriasis-like inflammatory response via the inhibition of c-Myc expression in keratinocytes.

Tunneling nanotubes (TNTs) are membranous structures that enable direct intercellular transfer of mitochondria, proteins, RNAs, and signaling molecules, playing key roles in tissue repair, immune coordination, and stress adaptation. Among their critical functions, TNT-mediated mitochondrial transfer rescues metabolically impaired cells, yet the regulatory mechanisms governing TNT formation and function remain incompletely understood. Recent studies highlight the Wnt signaling pathway-a conserved regulator of cell fate, polarity, and cytoskeletal remodeling-as a central modulator of TNT dynamics. Through its canonical (Wnt/β-catenin) and non-canonical (Wnt/PCP and Wnt/Ca) branches, Wnt signaling orchestrates actin filament organization, bundling, and turnover, all of which are essential for TNT biogenesis and stability. This review critically examines the mechanistic intersection between Wnt signaling and TNTs, with an emphasis on how Wnt-driven cytoskeletal remodeling supports intercellular connectivity. Beyond basic mechanistic insights, we also explore the physiological and pathological relevance of this crosstalk-including its roles in tissue regeneration, immune modulation, cancer progression, and neurodegeneration. While the Wnt-TNT axis offers therapeutic promise, its context-dependent effects demand careful consideration.

Interplay between tunneling nanotubes and Wnt Signaling: Insights into cytoskeletal regulation and therapeutic potential.

Inflammatory skin diseases such as psoriasis, atopic dermatitis, vitiligo, and lupus erythematosus present persistent therapeutic challenges due to their chronic nature, immune dysregulation, and suboptimal treatment outcomes. Stem cell-derived exosomes have emerged as a promising cell-free therapeutic approach, capable of modulating immune responses, promoting tissue regeneration, and restoring skin homeostasis. This review provides a comprehensive overview of exosomes derived from various stem cell sources-including adipose tissue, bone marrow, umbilical cord, dental pulp, and induced pluripotent stem cells-and their roles in regulating immune cell function and facilitating skin repair. Particular emphasis is placed on biomaterial-assisted delivery strategies, such as hydrogels, nanoparticles, and engineered scaffolds, which enhance the stability, targeting, and retention of exosomes at inflammatory sites. Key immunomodulatory mechanisms, including Treg/Th17 balance, macrophage polarization, and dendritic cell regulation, are also discussed. Finally, we highlight emerging preclinical and clinical evidence supporting the integration of exosome therapy with bioactive materials as a next-generation strategy for treating inflammatory skin disorders with improved precision and durability.

Biomaterial-enhanced delivery of stem cell-derived exosomes for skin inflammatory diseases: Mechanisms and therapeutic advances.

Oral mucosal wounds heal faster and with minimal scarring compared to skin injuries, yet the underlying mechanisms remain poorly understood. To explore the cellular and molecular basis of this difference, we performed single-cell RNA sequencing (scRNA-seq) on paired, uninjured human oral mucosa and skin tissues from the same donors. This approach enabled the construction of a comprehensive single-cell transcriptomic atlas, facilitating direct comparison of cellular composition, gene expression profiles, and intercellular communication between the two tissues. Our analysis revealed distinct tissue-specific heterogeneity among keratinocytes, fibroblasts, immune cells, and endothelial cells. Oral keratinocytes exhibited signatures associated with proliferation and metabolic activity, while oral fibroblasts and immune cells expressed gene profiles suggestive of pro-regenerative and anti-fibrotic functions. Cell-cell communication analysis indicated that endothelial cells in oral mucosa participate in interactions that may promote rapid tissue remodeling. Although our data were derived from uninjured tissues, the identified differentially expressed genes and enriched pathways suggest potential regulatory networks that may underlie the distinct wound-healing behaviors of oral mucosa and skin. A subset of these genes was validated by RT-PCR in both autologous and allogeneic samples across different age and sex groups, confirming the robustness and reproducibility of our findings. This study provides the first single-cell transcriptomic comparison of intact human oral mucosa and skin under steady-state conditions, establishing a foundational atlas that reveals intrinsic tissue-specific features and identifies candidate targets for promoting scarless healing.

ArticleTotal : 2	Year
Publication title	2026
Publication title	2026

Article	Year
Topical application of phenformin ameliorates the psoriasis-like inflammatory response via the inhibition of c-Myc expression in keratinocytes. Biochemical and biophysical research communications\| PubMed ID: 39121669	2024
Interplay between tunneling nanotubes and Wnt Signaling: Insights into cytoskeletal regulation and therapeutic potential. Biochemistry and biophysics reports\| PubMed ID: 40510685	2025
Biomaterial-enhanced delivery of stem cell-derived exosomes for skin inflammatory diseases: Mechanisms and therapeutic advances. International journal of biological macromolecules\| PubMed ID: 40516725	2025
Single-Cell transcriptomic analysis reveals distinct cellular and molecular signatures of human oral mucosa and skin. Cellular and molecular life sciences : CMLS\| PubMed ID: 41483202	2026

Tengfei Feng

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