Analysis of dermal fibroblasts isolated from neonatal and child cleft lip and adult skin: Developmental implications on reconstructive surgery

Abstract

The nonsyndromic cleft is one of the most frequent congenital defects in humans. Clinical data demonstrated improved and almost scarless neonatal healing of reparative surgery. Based on our previous results on crosstalk between neonatal fibroblasts and adult keratinocytes, the present study focused on characterization of fibroblasts prepared from cleft lip tissue samples of neonates and older children, and compared them with samples isolated from normal adult skin (face and breast) and scars. Although subtle variances in expression profiles of children and neonates were observed, the two groups differed significantly from adult cells. Compared with adult cells, differences were observed in nestin and smooth muscle actin (SMA) expression at the protein and transcript level. Furthermore, fibroblast to myofibroblast differentiation drives effective wound healing and is largely regulated by the cytokine, transforming growth factor-β1 (TGF-β1). Dysregulation of the TGF-β signalling pathway, including low expression of the TGF-β receptor II, may contribute to reducing scarring in neonates. Fibroblasts of facial origin also exhibited age independent differences from the cells prepared from the breast, reflecting the origin of the facial cells from neural crest-based ectomesenchyme.

The Head and Neck Squamous Cell Carcinoma Microenvironment as a Potential Target for Cancer Therapy

“…On the other hand, normal tissue fibroblasts from different body sites also broadly differ, e.g., normal fibroblasts from oral mucosa differ from the fibroblasts prepared from the skin (Figure 4). Clear differences between normal fibroblasts from the head and body and between fibroblasts of young and elderly patients were also observed [25].…”

Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

“…Is it maintained in the cultures, and for how long? If so, should we also take ageing into account in these models [ 33 ]?…”

Granulation tissue myofibroblasts during normal and pathological skin healing: The interaction between their secretome and the microenvironment

“…The secretion of certain cytokines by scar fibroblasts expressing α-SMA has been compared with the cytokine secretion of normal human skin fibroblasts in culture models 16 : while TGFß1 is believed to be the key stimulator of the matrix production by dermal cells during healing, the authors cannot detect any difference in the secretion of TGFß1 and TGFß2, interleukin (IL)-6 and IL-8 by myofibroblasts. On the other hand, the secretion of TGFß3 by scar fibroblasts is increased and the secretion of TGFα is decreased.…”

“…Aside from these chemokines, the main IL detected in the myofibroblast secretome is IL-6 16 (Figure 4). As explained by Johnson et al, 36 this cytokine is known to stimulate the migration of fibroblasts to the injury site, thus increasing the number of matrix-producing cells such as myofibroblasts.…”

“…As of yet not studied in detail, myofibroblasts secrete factors that can stimulate re-epithelialization, such as TGFα 16 and GM-CSF. 23 It has also been determined that in mice, myofibroblasts can convert to adipogenic precursors and, in the end, regenerate the hypodermis.…”