The basement membrane microenvironment directs the normalization and survival of bioengineered human skin equivalents

Nadav Segal, Frank Andriani, Lawrence Pfeiffer, Padmaja Kamath, Ning Lin, Kapettu Satyamurthy, Christophe Egles, Jonathan A Garlick

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Epithelial-mesenchymal interactions promote the morphogenesis and homeostasis of human skin. However, the role of the basement membrane (BM) during this process is not well-understood. To directly study how BM proteins influence epidermal differentiation, survival and growth, we developed novel 3D human skin equivalents (HSEs). These tissues were generated by growing keratinocytes at an air-liquid interface on polycarbonate membranes coated with individual matrix proteins (Type I Collagen, Type IV Collagen or fibronectin) that were placed on contracted Type I Collagen gels populated with dermal fibroblasts. We found that only keratinocytes grown on membranes coated with the BM protein Type IV Collagen showed optimal tissue architecture that was similar to control tissues grown on de-epidermalized dermis (AlloDerm) that contained intact BM. In contrast, tissues grown on proteins not found in BM, such as fibronectin and Type I Collagen, demonstrated aberrant tissue architecture that was linked to a significant elevation in apoptosis and lower levels of proliferation of basal keratinocytes. While all tissues demonstrated a normalized, linear pattern of deposition of laminin 5, tissues grown on Type IV Collagen showed elevated expression of alpha6 integrin, Type IV Collagen and Type VII Collagen, suggesting induction of BM organization. Keratinocyte differentiation (Keratin 1 and filaggrin) was not dependent on the presence of BM proteins. Thus, Type IV Collagen acts as a critical microenvironmental factor in the BM that is needed to sustain keratinocyte growth and survival and to optimize epithelial architecture.

    Original languageEnglish
    Pages (from-to)163-70
    Number of pages8
    JournalMatrix Biology
    Volume27
    Issue number3
    DOIs
    Publication statusPublished - 04-2008

    Fingerprint

    Basement Membrane
    Collagen Type IV
    Keratinocytes
    Skin
    Survival
    Fibronectins
    Membrane Proteins
    polycarbonate
    Integrin alpha6
    Keratin-1
    Collagen Type VII
    Choristoma
    Membranes
    Dermis
    Growth
    Morphogenesis
    Proteins
    Homeostasis
    Collagen
    Fibroblasts

    Cite this

    Segal, Nadav ; Andriani, Frank ; Pfeiffer, Lawrence ; Kamath, Padmaja ; Lin, Ning ; Satyamurthy, Kapettu ; Egles, Christophe ; Garlick, Jonathan A. / The basement membrane microenvironment directs the normalization and survival of bioengineered human skin equivalents. In: Matrix Biology. 2008 ; Vol. 27, No. 3. pp. 163-70.
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    The basement membrane microenvironment directs the normalization and survival of bioengineered human skin equivalents. / Segal, Nadav; Andriani, Frank; Pfeiffer, Lawrence; Kamath, Padmaja; Lin, Ning; Satyamurthy, Kapettu; Egles, Christophe; Garlick, Jonathan A.

    In: Matrix Biology, Vol. 27, No. 3, 04.2008, p. 163-70.

    Research output: Contribution to journalArticle

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    AU - Andriani, Frank

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