Paracrine anti‐fibrotic effects of neonatal cells and living cell constructs on young and senescent human dermal fibroblasts

Pratsinis, Harris; Armatas, Andreas A.; Dimozi, Anastasia; Lefaki, Maria; Vassiliu, Pantelis; Kletsas, Dimitris

doi:10.1111/wrr.12110

Cited by 19 publications

(8 citation statements)

References 43 publications

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“…The production of both fibronectin and tenascin by fibroblasts isolated from newborns seems to be lower compared to control fibroblasts of older donors. This result confirms antifibrotic activity of neonatal fibroblasts reported by others (Pratsinis et al 2013). These finding can also illustrate the reduced scar formation observed by us in newborns undergoing surgery during the first 10 days of life.…”

Section: Discussionsupporting

confidence: 92%

In Vitro Differences of Neonatal and Later Postnatal Keratinocytes and Dermal Fibroblasts

Krejčí

Kodet²,

Szabó³

et al. 2015

Physiol Res

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Skin healing process is postnatally always associated with scarring of various extent. Based on the clinical experience of plastic surgeons, the healing after lip cleft reconstruction is surprisingly almost scar-less when it is carried out within a few first days after birth. This phenomenon is not seen in delayed cases. In order to decipher causative mechanism, we have isolated and studied principal cell populations, keratinocytes and fibroblast, from residual tissue samples after reconstructive operation (N=39) performed at various age (0-9 years). These cells play the pivotal role in the healing and that is why we focused on description of their phenotype and also functionality with respect to age. We have identified a population of remarkably small cells in explants from newborns (day 0-10).These small cells were strongly positive for markers of low differentiated keratinocytes, keratin-8 and -19, and moreover also for vimentin. In the explants cultures from older babies this population was missing. Fibroblasts from newborns and older patients differed namely in terms of nestin expression and also in the production of extracellular matrix components. We conclude that in vitro described properties of keratinocytes and fibroblasts in newborns could participate on the almost scar-less wound healing in earliest neonatal period.

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Section: Discussionsupporting

confidence: 92%

In Vitro Differences of Neonatal and Later Postnatal Keratinocytes and Dermal Fibroblasts

Krejčí

Kodet²,

Szabó³

et al. 2015

Physiol Res

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“…The age of the cell donor thus represents a very important parameter influencing the behavior of cells in vitro and it also affects the course of wound healing after grafting. An observed antifibrotic effect of NFs ( 40 ) as well as expression profiles of human fibroblasts performed by us and others ( 41 ) support these findings.…”

Section: Discussionsupporting

confidence: 68%

Functional differences between neonatal and adult fibroblasts and keratinocytes: Donor age affects epithelial-mesenchymal crosstalk in vitro

Mateu

Živicová

Krejčí

et al. 2016

International Journal of Molecular Medicine

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Clinical evidence suggests that healing is faster and almost scarless at an early neonatal age in comparison with that in adults. In this study, the phenotypes of neonatal and adult dermal fibroblasts and keratinocytes (nestin, smooth muscle actin, keratin types 8, 14 and 19, and fibronectin) were compared. Furthermore, functional assays (proliferation, migration, scratch wound closure) including mutual epithelial-mesenchymal interactions were also performed to complete the series of experiments. Positivity for nestin and α smooth muscle actin was higher in neonatal fibroblasts (NFs) when compared with their adult counterparts (adult fibroblasts; AFs). Although the proliferation of NFs and AFs was similar, they significantly differed in their migration potential. The keratinocyte experiments revealed small, poorly differentiated cells (positive for keratins 8, 14 and 19) in primary cultures isolated from neonatal tissues. Moreover, the neonatal keratinocytes exhibited significantly faster rates of healing the experimentally induced in vitro defects in comparison with adult cells. Notably, the epithelial/mesenchymal interaction studies showed that NFs in co-culture with adult keratinocytes significantly stimulated the adult epithelial cells to acquire the phenotype of small, non-confluent cells expressing markers of poor differentiation. These results indicate the important differences between neonatal and adult cells that may be associated with improved wound healing during the early neonatal period.

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“…Notably, adult keratinocytes acquire properties of neonatal keratinocytes, including the occurrence of very small ones under their influence ( 23 ). This result is supported by the observation that the neonatal fibroblasts, as well as their products, exert a distinct anti-fibrotic effect ( 19 , 24 ). This broad activity is to be expected, as fibroblasts are drivers of the embryonic development of epidermal appendages.…”

Section: Introductionmentioning

confidence: 52%

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

Živicová

Lacina

Mateu

et al. 2017

International Journal of Molecular Medicine

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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.

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Paracrine anti‐fibrotic effects of neonatal cells and living cell constructs on young and senescent human dermal fibroblasts

Cited by 19 publications

References 43 publications

In Vitro Differences of Neonatal and Later Postnatal Keratinocytes and Dermal Fibroblasts

In Vitro Differences of Neonatal and Later Postnatal Keratinocytes and Dermal Fibroblasts

Functional differences between neonatal and adult fibroblasts and keratinocytes: Donor age affects epithelial-mesenchymal crosstalk in vitro

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

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