Keratinocyte Migration is Affected by Fibroblast Subtype
Erin L. Weber, MD PhD, Warren L. Garner, MD, Cheng Ming Chuong, MD PhD.
University of Southern California, Los Angeles, CA, USA.
PURPOSE: Chronic wounds affect 6 million people in the United States alone and are challenging to treat, leading to prolonged debility. Wound healing is a complex process requiring an inflammatory response, fibroblast proliferation, matrix production, and keratinocyte migration to close the wound. While keratinocytes at the edge of a chronic wound are highly proliferative, they fail to migrate. We hypothesize that papillary fibroblasts present at the exposed surface of a superficial, easily healable, wound stimulate keratinocyte migration more effectively than reticular fibroblasts present at the exposed surface of a deep or chronic wound. Identification of factors which enhance keratinocyte migration could provide new treatment for chronic wounds.
METHODS: Site-matched human keratinocytes and dermal fibroblasts were isolated from discarded skin during surgery. Papillary and reticular fibroblasts were cultured separately. Keratinocytes were grown on an insert and migration was assessed using a standard scratch assay with keratinocytes exposed to media, papillary, or reticular fibroblasts.
RESULTS: Fibroblast type dramatically affected epithelial migration. Keratinocytes exposed to papillary fibroblasts exhibited a 58% closure of the scratch over 8 hours while reticular fibroblasts stimulated a 73% reduction (p=0.02). When exposed to mixed cultures containing both fibroblast subtypes, keratinocytes closed the scratch by 88%. Keratinocytes subjected to media alone demonstrated a basal migration of 36%.
CONCLUSION: These data provide strong evidence for how cells interact in the wound environment to optimize healing. Studies are ongoing to identify secreted factors which mediate enhanced keratinocyte migration. Future experiments will consider dysfunctional support of epithelial migration by chronic wound fibroblasts.
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