title: Wound-healing gene family expression differences between fetal and foreskin cells used for bioengineered skin substitutes.
abstract: For tissue engineering, several cell types and tissues have been proposed as starting material. Allogenic skin products available for therapeutic usage are mostly developed with cell culture and with foreskin tissue of young individuals. Fetal skin cells offer a valuable solution for effective and safe tissue engineering for wounds due to their rapid growth and simple cell culture. By selecting families of genes that have been reported to be implicated in wound repair and particularly for scarless fetal wound healing including transforming growth factor-beta (TGF-beta) superfamily, extracellular matrix, and nerve/angiogenesis growth factors, we have analyzed differences in their expression between fetal skin and foreskin cells, and the same passages. Of the five TGF-beta superfamily genes analyzed by real-time reverse transcription-polymerase chain reaction, three were found to be significantly different with sixfold up-regulated for TGF-beta2, and 3.8-fold for BMP-6 in fetal cells, whereas GDF-10 was 11.8-fold down-regulated. For nerve growth factors, midkine was 36-fold down-regulated in fetal cells, and pleiotrophin was 4.76-fold up-regulated. We propose that fetal cells present technical and therapeutic advantages compared to foreskin cells for effective cell-based therapy for wound management, and overall differences in gene expression could contribute to the degree of efficiency seen in clinical use with these cells.
authors.affiliation: Department of Pediatric Surgery, University Hospital, CHUV, Lausanne, Switzerland. Lee.Laurent-Applegate@chuv.ch
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hirt-Burri
authors.forename: Corinne
authors.initials: C
authors.lastname: Scaletta
authors.forename: Stefan
authors.initials: S
authors.lastname: Gerber
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Pioletti
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Applegate
mesh_terms: D055398:Bone Morphogenetic Protein 3; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D017690:Cell Transplantation; D016207:Cytokines / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D052816:Foreskin / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D055413:Growth Differentiation Factor 10; D006801:Humans; D008297:Male; D000078792:Midkine; D005810:Multigene Family; D009414:Nerve Growth Factors / Q000235:genetics; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D016038:Skin Transplantation; D017768:Skin, Artificial; D046509:Tissue Culture Techniques; D023822:Tissue Engineering; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
chemical_list: C525757:BMP3 protein, human; C525816:BMP6 protein, human; D055398:Bone Morphogenetic Protein 3; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D016207:Cytokines; C525785:GDF10 protein, human; D055413:Growth Differentiation Factor 10; D009414:Nerve Growth Factors; D053781:Transforming Growth Factor beta2; C066845:pleiotrophin; D000078792:Midkine; D012313:RNA