title: A Dermal Equivalent Engineered with TGF-β3 Expressing Bone Marrow Stromal Cells and Amniotic Membrane: Cosmetic Healing of Full-Thickness Skin Wounds in Rats.
abstract: Transforming growth factor beta-3 (TGF-β3) has been shown to decrease scar formation after scheduled topical applications to the cutaneous wounds. This study aimed to continuously deliver TGF-β3, during the early phase of wound healing, by engineering a dermal equivalent (DE) using TGF-β3 expressing bone marrow stromal cells (BM-SCs) and human dehydrated amniotic membrane (hDAM). To engineer a DE, rat BM-SCs were seeded on the hDAM and TGF-β3 was transiently transfected into the BM-SCs using a plasmid vector. Pieces of the dermal equivalent were transplanted onto the full-thickness excisional skin wounds in rats. The process of wound healing was assessed by image analysis, Manchester Scar Scale (MSS), and histopathological studies 7, 14, 21, and 85 days after the excision. The results confirmed accurate construction of recombinant pcDNA3.1-TGF-β3 expression system and showed that the transfected BM-SCs seeded on hDAM expressed TGF-β3 mRNA and protein from day 3 through day 7 after transfection. After implantation of the DE, contraction of the wounds was measured from day 7 through 21 and analyzed by linear regression, which revealed that the rate of wound contraction in all experimental groups was similar. Histologic evaluation demonstrated that transfected BM-SCs decreased retention and recruitment of the cells during the early stage of wound healing, decreased the formation of vascular structures and led to formation of uniformly parallel collagen bundles. MSS scores showed that TGF-β3 secreting cells significantly improved the cosmetic appearance of the healed skin and decreased the scar formation. From these results, it could be concluded that transient secretion of TGF-β3, during the early phase of healing, by BM-SCs seeded on hDAM can improve the cosmetic appearance of the scar in cutaneous wounds without negatively affecting the process of wound repair.
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences.|Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences.|Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran.
authors.forename: Ali
authors.initials: A
authors.lastname: Samadikuchaksaraei
authors.affiliation: Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mehdipour
authors.affiliation: Department of Medical Biotechnology, Faculty of Allied Medicine, Guilan University of Medical Sciences, Rasht.
authors.forename: Mehryar
authors.initials: M
authors.lastname: Habibi Roudkenar
authors.affiliation: Department of Applied Cellular Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences.
authors.forename: Javad
authors.initials: J
authors.lastname: Verdi
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Joghataei
authors.affiliation: Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: As'adi
authors.affiliation: Department of Medical Biotechnology, Faculty of Allied Medicine, Guilan University of Medical Sciences, Rasht.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Amiri
authors.affiliation: Translational Oncology, Department of Hematology, Oncology, Immunology, Rheumatology and Pulmonology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Dehghan Harati
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences.|Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences.|Department of Medical Biotechnology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences.
authors.forename: Mazaher
authors.initials: M
authors.lastname: Gholipourmalekabadi
authors.affiliation: Eposcience Millennium Institute, Tehran, Iran.
authors.forename: Nushin
authors.initials: N
authors.lastname: Karkuki Osguei
mesh_terms: D000650:Amnion / Q000737:chemistry* / Q000166:cytology; D000818:Animals; D001705:Bioprosthesis; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000293:injuries / Q000473:pathology* / Q000648:ultrastructure; D017768:Skin, Artificial; D054457:Tissue Scaffolds / Q000737:chemistry*; D014162:Transfection; D053782:Transforming Growth Factor beta3 / Q000235:genetics*; D014945:Wound Healing
chemical_list: D053782:Transforming Growth Factor beta3
keywords: Cicatrix; Keloid; Re-epithelialization; Scar; Transforming growth factor beta-3