Clonal characterization of fibroblasts in the superficial layer of the adult human dermis

Abstract

The dermis of adult human skin contains a physiologically heterogeneous population of fibroblasts that interact to produce its unique architecture and that participate in inflammatory and wound repair functions in vivo. This heterogeneity has been well documented for fibroblasts located in the superficial papillary dermis and the deep reticular dermis. However, the existence of diverse fibroblast subpopulations within a given region of the dermis has not been explored. In this study, fibroblast cultures have been established from the superficial dermis following enzymatic dissociation of the tissue. These fibroblasts have been cloned by limiting dilution and initially selected on the basis of morphology and proliferation kinetics. Fibroblasts in some of the clones selected for study express alpha-smooth muscle actin, a myofibroblast characteristic. Significant differences for fibroblast clones obtained from the same piece of skin have been observed with regard to their rate of collagen lattice contraction, their ability to organize a fibronectin matrix, their release of specific growth factors/cytokines into culture medium, and their response to interleukin-1alpha. These differences in both morphological and physiological characteristics indicate that the superficial papillary dermis contains a heterogeneous population of fibroblasts. This heterogeneity might indicate that diverse subpopulations of fibroblasts are required to interact in both homeostatic and pathological situations in skin.

Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

“…Additionally, skin fibroblasts are heterogeneous, with distinct populations localized in the upper and lower dermis. [67][68][69] The relative responsiveness of these different subpopulations to collagen fragmentation is not known.…”

Multifocal epithelial tumors and field cancerization: stroma as a primary determinant

“…Fibroblast populations from various body parts and within individual organs can have significantly different properties, including susceptibility to CAF phenotype acquisition and interactions with neighboring epithelial cells and cells of the immune/inflammatory system (119-123). These differences, and/ or underlying gene expression signature, are rather stable and maintained with cultivation (124)(125)(126)(127).…”

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

“…In skin dermis, for example, different dermal layers host diverse subpopulations of fibroblasts with both unique morphologies and physiologic functions. [5][6][7][8] Depending on their resident depth of dermis, fibroblasts express different quantities of collagen and ratios of collagen type I and III mRNA. Further, fibroblasts within the deeper dermis produce less collagenase mRNA than do fibroblasts in more superficial layers.…”