据一篇发表在11月21日Lancet杂志的研究报告，I-STEM*研究所(I-STEM/ Inserm UEVE U861/AFM)由Marc Peschanski主持的课题组成功地利用人类胚胎干细胞生成一块完整的表皮。课题组希望未来可以利用这种干细胞作为治疗三度烧伤患者和遗传性皮肤病患者的可替代疗法。
人类胚胎干细胞(Human embryonic stem cells,hES)有两个基本特征：无限增殖的能力和分化为机体各种细胞的多能性。
首先，课题组获得皮肤干细胞——角质生成细胞(keratinocytes)，角质生成细胞可以使皮肤得到不断更新；然后研究人员先后分别在体外和生物体上测试分离出来的角质生成细胞重组形成功能性表皮细胞的能力。
在细胞生物学和药理学方法的支持下，使hES细胞转化为表皮细胞成为可能。研究人员在体外成功地利用角质生成细胞重建出来一块表皮(epidermis)，最后，研究人员还需要正式这种在体外获得的成果可以转移到生物体上。在该试验的最后阶段，研究人员将获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肤区域完全恢复正常。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
