據(jù)一篇發(fā)表在11月21日Lancet雜志的研究報(bào)告,，I-STEM*研究所(I-STEM/ Inserm UEVE U861/AFM)由Marc Peschanski主持的課題組成功地利用人類胚胎干細(xì)胞生成一塊完整的表皮,。課題組希望未來(lái)可以利用這種干細(xì)胞作為治療三度燒傷患者和遺傳性皮膚病患者的可替代療法。
人類胚胎干細(xì)胞(Human embryonic stem cells,hES)有兩個(gè)基本特征：無(wú)限增殖的能力和分化為機(jī)體各種細(xì)胞的多能性,。
首先,，課題組獲得皮膚干細(xì)胞——角質(zhì)生成細(xì)胞(keratinocytes)，角質(zhì)生成細(xì)胞可以使皮膚得到不斷更新,；然后研究人員先后分別在體外和生物體上測(cè)試分離出來(lái)的角質(zhì)生成細(xì)胞重組形成功能性表皮細(xì)胞的能力,。
在細(xì)胞生物學(xué)和藥理學(xué)方法的支持下,，使hES細(xì)胞轉(zhuǎn)化為表皮細(xì)胞成為可能。研究人員在體外成功地利用角質(zhì)生成細(xì)胞重建出來(lái)一塊表皮(epidermis),，最后,，研究人員還需要正式這種在體外獲得的成果可以轉(zhuǎn)移到生物體上。在該試驗(yàn)的最后階段,，研究人員將獲得的表皮移植到免疫能力降低的小鼠上,，移植后12周，小鼠移植表皮的局部皮膚區(qū)域完全恢復(fù)正常,。（生物谷Bioon.com）
生物谷推薦原始出處：
The Lancet, Volume 374, Issue 9703, Pages 1745 - 1753, 21 November 2009
Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study
Hind Guenou PhD a, Xavier Nissan a, Fernando Larcher PhD b, Jessica Feteira a, Gilles Lemaitre PhD a, Manoubia Saidani a, Marcela Del Rio PhD b, Christine C Barrault c, Fran?ois-Xavier Bernard PhD c, Marc Peschanski MD a, Dr Christine Baldeschi PhD a , Prof Gilles Waksman PhD a
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.
Funding
Institut National de la Santé et de la Recherche Médicale, University Evry Val d'Essonne, Association Fran?aise contre les Myopathies, Fondation René Touraine, and Genopole.
