Genomics

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Expression profile of grafted human engineered skin substitutes compared with intact human


ABSTRACT: The goal of the experiment: To characterize the dynamic gene expression profile of engineered human skin in vitro and after grafting, and compare with expression profile of uninjured human skin. Bioengineered skin substitutes can facilitate wound closure in massively burned patients, but deficiencies limit their outcomes compared to native skin autografts. To identify gene programs associated with their in vivo capabilities and limitations, we extended previous gene expression profile analyses to now compare engineered skin following in vivo grafting to both in vitro maturation and to normal human skin. Cultured skin substitutes were grafted to full-thickness wounds in athymic mice; biopsies for microarray analyses were collected at multiple in vitro and in vivo time points. Over 10,000 transcripts exhibited large-scale expression pattern differences during in vitro and in vivo maturation. Using hierarchical clustering, eleven different expression profile clusters were partitioned based on differential sample type and temporal stage-specific activation or repression. Analyses show that the wound environment exerts a massive influence on gene expression in skin substitutes. For example, in vivo healed skin substitutes gained expression of many native skin-expressed genes, including those associated with epidermal barrier and multiple categories of cell-cell and cell-basement membrane adhesion. In contrast, immunologic, trichogenic, and endothelial gene programs were largely lacking. These analyses suggest important areas to guide further improvement of engineered skin for both increased homology with native skin and enhanced wound healing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17539 | GEO | 2009/08/07

SECONDARY ACCESSION(S): PRJNA118647

REPOSITORIES: GEO

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