Enhanced Vascularization of Cultured Skin Substitutes Genetically Modified to Overexpress Vascular Endothelial Growth Factor11The authors declared in writing to have no conflict of interest.

Supp, Dorothy M.; Supp, Andrew P.; Boyce, Steven T.; Bell, Sheila M.

doi:10.1046/j.1523-1747.2000.00824.x

Cited by 120Wound Healing and TreatmentsTissue Engineering and Regenerative MedicineAngiogenesis and VEGF in Cancer

Enhanced Vascularization of Cultured Skin Substitutes Genetically Modified to Overexpress Vascular Endothelial Growth Factor11The authors declared in writing to have no conflict of interest.

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Supp, Dorothy M., Supp, Andrew P., Boyce, Steven T., Bell, Sheila M.·2000·Journal of Investigative Dermatology

DOI 10.1046/j.1523-1747.2000.00824.x

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Abstract

Cultured skin substitutes have been used as adjunctive therapies in the treatment of burns and chronic wounds, but they are limited by lack of a vascular plexus. This deficiency leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Genetic modification of cultured skin substitutes to enhance vascularization could hypothetically lead to improved wound healing. To address this hypothesis, human keratinocytes were genetically modified by transduction with a replication incompetent retrovirus to overexpress vascular endothelial growth factor, a specific and potent mitogen for endothelial cells. Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates inoculated with human fibroblasts and either vascular endothelial growth factor-modified or control keratinocytes were prepared, and were cultured in vitro for 21 d. Northern blot analysis demonstrated enhanced expression of vascular endothelial growth factor mRNA in genetically modified keratinocytes and in cultured skin substitutes prepared with modified cells. Furthermore, the vascular endothelial growth factor-modified cultured skin substitutes secreted greatly elevated levels of vascular endothelial growth factor protein throughout the entire culture period. The bioactivity of vascular endothelial growth factor protein secreted by the genetically modified cultured skin substitutes was demonstrated using a microvascular endothelial cell growth assay.…

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There has been a complete absence of an endogenously differentiating vascularized, hair-bearing human skin equivalent that contains immune cell populations.
“While many attempts to generate complex 3D skin equivalents have achieved vascularization, hair follicle generation, and immune cell co‐cultures, there has been a complete absence of endogenously differentiating a vascularized, hair‐bearing human skin equivalent that contains immune cell populations.[ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [22]

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Authors: Supp, D. M., Supp, A. P., Boyce, S. T., & Bell, S. M.
Affiliations: Shriners Hospitals for Children - Cincinnati (US)
Cincinnati Children's Hospital Medical Center (US)
Corresponding author: Boyce, Steven T.
ORCID: Supp, Dorothy M.
Boyce, Steven T.
Bell, Sheila M.
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2000-01
Volume: 114
Issue: 1
Pages: 5-13
ISSN: 0022-202X (ISSN-L)
DOI: 10.1046/j.1523-1747.2000.00824.x
OpenAlex: W2010067741
Cited by: 120
References: 38
Citations by year: 2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 5
FWCI: 10.45
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5814 d)
Locations: Journal of Investigative Dermatology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: cultured skin substitutes, vascular endothelial growth factor, retroviral transduction, graft vascularization, wound healing, burns, chronic wounds, skin blood vessels, full-thickness skin graft, athymic mice
MeSH terms: Animals, Blood Vessels, Cells, Cultured, Collagen, Fibroblasts, Genetic Techniques, Glycosaminoglycans, Humans, Lymphokines, Mice, Nude, RNA, Messenger, Skin, Wounds and Injuries, Keratinocytes, Endothelial Growth Factors, Skin, Artificial, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice

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Enhanced Vascularization of Cultured Skin Substitutes Genetically Modified to Overexpress Vascular Endothelial Growth Factor11The authors declared in writing to have no conflict of interest.

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