Wednesday, December 2, 2009

Scientists Grow Skin Tissue in Preclinical Study

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A team of researchers from France and Spain managed to grow complete human skin epidermis from skin-derived stem cells on laboratory mice. The finding could lead to the rapid production of one's own skin patches for people with burns and other severe skin problems.

From the article abstract in The Lancet:

Background

Cell therapy for large burns is dependent upon autologous epidermis reconstructed in vitro. However, the effectiveness of current procedures is limited by the delay needed to culture the patient's own keratinocytes. To assess whether the keratinocyte progeny of human embryonic stem cells (hESCs) could be used to form a temporary skin substitute for use in patients awaiting autologous grafts, we investigated the cells' capability of constructing a pluristratified epidermis.

Methods

hESCs from lines H9 and SA01 were seeded at least in triplicate on fibroblast feeder cells for 40 days in a medium supplemented with bone morphogenetic protein 4 and ascorbic acid. Molecular characterisation of cell differentiation was done throughout the process by quantitative PCR, fluorescence-activated cell sorting, and immunocytochemical techniques. Keratinocyte molecular differentiation and functional capacity to construct a human epidermis were assessed in vitro and in vivo.

Findings

From hESCs, we generated a homogeneous population of cells that showed phenotypic characteristics of basal keratinocytes. Expression levels of genes encoding keratin 14, keratin 5, integrin α6, integrin β4, collagen VII, and laminin 5 in these cells were similar to those in basal keratinocytes. After seeding on an artificial matrix, keratinocytes derived from hESCs (K-hESCs) formed a pluristratified epidermis. Keratin-14 immunostaining was seen in the basal compartment, with keratin 10 present in layers overlying the basal layer. Involucrin and filaggrin, late markers of epidermal differentiation, were detected in the uppermost layers only. 12 weeks after grafting onto five immunodeficient mice, epidermis derived from K-hESCs had a structure consistent with that of mature human skin. Human involucrin was appropriately located in spinous and granular layers and few Ki67-positive cells were detected in the basal layer.

Interpretation

hESCs can be differentiated into basal keratinocytes that are fully functional—ie, able to construct a pluristratified epidermis. This resource could be developed to provide temporary skin substitutes for patients awaiting autologous grafts.

Here's a Lancet podcast discussing the research with two of the study authors, Marc Peschanski MD and Dr Christine Baldeschi PhD of the Institute for Stem Cell Therapy and Exploration of Monogenic diseases, Evry Cedex, France:

Abstract in The Lancet: Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study

File image: Wellcome Images

(hat tip: Birmingham Science News Examiner)

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