mouse-wound-models-and-preparation-of-single-cell-suspensions

Mouse Wound Models and Preparation of Single-Cell Suspensions

The management of acute full-thickness skin injuries presents a considerable challenge in clinical practice. The complexity of wound healing, involving ...

Medical School of Chinese People's Liberation Army

Full-thickness skin wound healing remains a serious undertaking for patients. While stem cell-derived exosomes have been proposed as a potential therapeutic approach, the underlying mechanism of action has yet to be fully elucidated. The current study aimed to investigate the impact of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exosomes) on the single-cell transcriptome of neutrophils and macrophages in the context of wound healing.

Human umbilical cord mesenchymal stem cell-derived exosomes promote murine skin wound healing by neutrophil and macrophage modulations revealed by single-cell RNA sequencing.

[This corrects the article DOI: 10.3389/fimmu.2023.1142088.].

Corrigendum: Human umbilical cord mesenchymal stem cell-derived exosomes promote murine skin wound healing by neutrophil and macrophage modulations revealed by single-cell RNA sequencing.

The potential of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hucMSC-EVs) in wound healing is promising, yet a comprehensive understanding of how fibroblasts and keratinocytes respond to this treatment remains limited. This study utilizes single-cell RNA sequencing (scRNA-seq) to investigate the impact of hucMSC-EVs on the cutaneous wound microenvironment in mice. Through rigorous single-cell analyses, we unveil the emergence of hucMSC-EV-induced hematopoietic fibroblasts and MMP13+ fibroblasts. Notably, MMP13+ fibroblasts exhibit fetal-like expressions of MMP13, MMP9, and HAS1, accompanied by heightened migrasome activity. Activation of MMP13+ fibroblasts is orchestrated by a distinctive PIEZO1-calcium-HIF1α-VEGF-MMP13 pathway, validated through murine models and dermal fibroblast assays. Organotypic culture assays further affirm that these activated fibroblasts induce keratinocyte migration via MMP13-LRP1 interactions. This study significantly contributes to our understanding of fibroblast heterogeneities as well as intercellular interactions in wound healing and identifies hucMSC-EV-induced hematopoietic fibroblasts as potential targets for reprogramming. The therapeutic targets presented by these fibroblasts offer exciting prospects for advancing wound healing strategies.

Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Induce Fetal Wound Healing Features Revealed by Single-Cell RNA Sequencing.

N6-Methyladenosine (mA) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of mA methylation in photoaging remains unknown.

Yuanyuan Liu

Medical School of Chinese People's Liberation Army

Mouse Wound Models and Preparation of Single-Cell Suspensions