Robust classification of wound healing stages in both mice and humans for acute and burn wounds based on transcriptomic data

Abstract

Background Wound healing involves careful coordination among various cell types carrying out unique or even multifaceted functions. The abstraction of this complex dynamic process into four primary wound stages is essential to the study of wound care for timing treatment and tracking wound progression. For example, a treatment that may promote healing in the inflammatory stage may prove detrimental in the proliferative stage. Additionally, the time scale of individual responses varies widely across and within the same species. Therefore, a robust method to assess wound stages can help advance translational work from animals to humans. Results In this work, we present a data-driven model that robustly identifies the dominant wound healing stage using transcriptomic data from biopsies gathered from mouse and human wounds, both burn and surgical. A training dataset composed of publicly available transcriptomic arrays is used to derive 58 shared genes that are commonly differentially expressed. They are divided into 5 clusters based on temporal gene expression dynamics. The clusters represent a 5-dimensional parametric space containing the wound healing trajectory. We then create a mathematical classification algorithm in the 5-dimensional space and demonstrate that it can distinguish between the four stages of wound healing: hemostasis, inflammation, proliferation, and remodeling. Conclusions In this work, we present an algorithm for wound stage detection based on gene expression. This work suggests that there are universal characteristics of gene expression in wound healing stages despite the seeming disparities across species and wounds. Our algorithm performs well for human and mouse wounds of both burn and surgical types. The algorithm has the potential to serve as a diagnostic tool that can advance precision wound care by providing a way of tracking wound healing progression with more accuracy and finer temporal resolution compared to visual indicators. This increases the potential for preventive action.

Ovulation provides excessive coagulation and hepatocyte growth factor signals to cause postoperative intraabdominal adhesions

“…According to previous studies including genome-wide comparisons of molecular changes during wound healing, the time scales of different stages (hemostasis, inflammation, proliferation, and remodeling) of wound healing after either surgical or burn injury was very similar in mouse and human. 30 Therefore, the time window to avoid ovulation to protect from adhesions should be similar in both mouse and human.…”

Plasma-Based Scaffold Containing Bone-Marrow Mononuclear Cells Promotes Wound Healing in a Mouse Model of Pressure Injury

“…At 3 days, the homeostasis and inflammation stage of wound repair is active in the mouse 29 . On Day 3, the percentage of wound reduction was macroscopically practically the same in all the treatment groups, only slightly higher for the ulcers treated with BM-MNC.…”

“…At 7 days, the proliferation stage is almost complete in the mouse 29 . When pressure ulcer specimens were analyzed on Day 7, the effects of treatment became more evident, with macroscopic differences observed between the three study groups.…”

“…Finally, at 14 days, the last stage of tissue repair involving wound contraction and remodeling is completed in the mouse 29 . On day 14, ulcers in this Plasma + BM-MNC group had practically resolved (90.617%), a rate that was higher than that observed in the remaining groups.…”

Wound Healing Promotion via Release of Therapeutic Metallic Ions from Phosphate Glass Fibers: An In Vitro and Ex Vivo Study

“…Timelines are only indicative because they can vary with the type of wound and stages can overlap. For acute wounds and burns, times of each stage can be shorter: hemostasis (up to 6 h), inflammation (up to 24 h), proliferation (∼ 3–7 days), and remodeling (∼ 7–21 days) . Various TMI have been found to be effective in promoting specific stages of wound healing (hemostasis, inflammation, proliferation, and remodeling).…”