| Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers. | |
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MedLine Citation:
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PMID: 12931279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bilayered living human skin equivalent (HSE) consists of cultured keratinocytes residing on the surface of a fibroblast-populated collagen lattice. Although HSE is FDA-approved for treatment of diabetic foot and venous stasis ulcers, its clinical efficacy remains limited, because the molecular mechanisms underlying its therapeutic effect are not fully understood. It is, therefore, often applied mistakenly as a skin graft. In this report, we delineate a mechanism of HSE biological effect and consequent optimal clinical use in accelerating closure of diabetic foot ulcers. Experimental: HSE was grafted onto nude mice and the release of various growth factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Clinical: HSE was grafted onto 11 consecutive patients with diabetes who had 13 non-ischemic foot ulcers and healing was measured as time to 100% closure (e.g., no drainage and 100% epithelialized). Experimental: HSE cellular components were determined to express 15 different growth factors/cytokine genes known to promote wound healing. Histological evidence from the nude mice showed that the collagen component of HSE underwent remodeling within the first seven days of grafting. Clinical: All diabetic foot ulcers healed in 31.8 12.4 days. Local release of a unique combination of 15 growth factors expressed by HSE keratinocyte and fibroblast components generates closure of diabetic foot ulcers. HSE should be applied with the same surgical conditions for a skin graft (i.e., no cellulitis, no drainage, and negligible bacteria). We hypothesize that bilayered HSE generates its effect by way of the local synthesis and release of multiple growth factors in specific combination and concentration, which improves the impaired reparative process of chronic wounds. |
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Authors:
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Harold Brem; Jan Young; Marjana Tomic-Canic; Cary Isaacs; H Paul Ehrlich |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: Surgical technology international Volume: 11 ISSN: 1090-3941 ISO Abbreviation: Surg Technol Int Publication Date: 2003 |
Date Detail:
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Created Date: 2003-08-21 Completed Date: 2004-05-19 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9604509 Medline TA: Surg Technol Int Country: United States |
Other Details:
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Languages: eng Pagination: 23-31 Citation Subset: IM |
Affiliation:
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Angiogenesis and Wound Healing Laboratory, Mount Sinai Medical Center, New York, NY, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Biopsy, Needle Cells, Cultured Clinical Trials as Topic Cytokines / metabolism Diabetic Foot / pathology*, surgery* Disease Models, Animal Fibroblasts / transplantation* Graft Survival Humans Immunohistochemistry Mice Molecular Sequence Data Polymerase Chain Reaction Risk Assessment Sensitivity and Specificity Severity of Illness Index Skin Transplantation / methods* Skin, Artificial* Tissue and Organ Harvesting / methods Treatment Outcome Wound Healing / physiology |
| Grant Support | |
ID/Acronym/Agency:
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AR 45974/AR/NIAMS NIH HHS; DK 59424/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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