Abstract
Burn injuries are a major global health concern, ranking as the fourth most common type of injury. Healing mechanisms defined in other wounds are often applied to burn wounds. However, documented effects of major trauma, such as burn injury, both immune responses and the skin itself suggest that burn wound healing mechanisms may be distinct and warrant further investigation.Cell types that have been shown to play a crucial role in wound healing are myofibroblasts, the predominant cell type in the wound dermis and adipose precursor cells, which may give rise to fibroblast subtypes. Myofibroblasts can be categorized into various subsets that can either promote repair or favor scar formation.
Thus, we sought to identify myofibroblast populations and their temporal profiles during burn wound injury. We aimed to examine whether specific subsets are present in burn wound healing compared to those documented in excision wounds.
We employed a mouse model of scald burn injury and isolated tissue during the proliferative phase; (day 14 and 21 post injury; d14 pi, d21 pi), and at wound closure (d28 pi). Tissues were analyzed via immunohistochemistry and flow cytometry. We employed previously established flow cytometric analysis to define fibrotic (CD45-CD31-CD26+) and non-fibrotic (CD45-CD31-CD26-) myofibroblasts. Spatial distribution of adipose precursors and myofibroblasts within wound beds was done by immunohistochemistry and by examining cells isolated from the wound beds via flow cytometry. Male and female mice were analyzed separately.
All subsets were present at the burn wound site during the healing process. In addition, we identified adipose precursor cells, (CD45-CD31-SCA1+CD34+CD29+), and CD29 myofibroblasts (CD45-CD31-SCA1-CD34-CD29+); all subsets were further subcategorized based on the CD26 and CD9 expression.
Here, we have established the presence of adipose derived mesenchymal stem cell subpopulations (ADMSCs) during burn wound healing. Adipose precursor and myofibroblast spatial and temporal profiles during burn wound healing exhibit heterogeneity and fluctuate throughout repair with differences in sex being present as well. Our investigation will allow us to better understand the dynamics and interactions of these cell populations and could lead to a better understanding of burn healing mechanisms.