Department of Dermatology, Columbia University, New York, NY, U.S.A.
Department of Bioengineering, Imperial College London, London, U.K.
Br J Dermatol. 2017 May;176(5):1259-1269. doi: 10.1111/bjd.15087. Epub 2017 Mar 14.
The method of generating bioengineered skin constructs was pioneered several decades ago; nowadays these constructs are used regularly for the treatment of severe burns and nonhealing wounds. Commonly, these constructs are comprised of skin fibroblasts within a collagen scaffold, forming the skin dermis, and stratified keratinocytes overlying this, forming the skin epidermis. In the past decade there has been a surge of interest in bioengineered skins, with researchers seeking alternative cell sources, or scaffolds, from which constructs can be established, and for more biomimetic equivalents with skin appendages.
To evaluate whether human hair follicle dermal cells can act as an alternative cell source for engineering the dermal component of engineered skin constructs.
We established in vitro skin constructs by incorporating into the collagenous dermal compartment: (i) primary interfollicular dermal fibroblasts, (ii) hair follicle dermal papilla cells or (iii) hair follicle dermal sheath cells. In vivo skins were established by mixing dermal cells and keratinocytes in chambers on top of immunologically compromised mice.
All fibroblast subtypes were capable of supporting growth of overlying epithelial cells, both in vitro and in vivo. However, we found hair follicle dermal sheath cells to be superior to fibroblasts in their capacity to influence the establishment of a basal lamina.
Human hair follicle dermal cells can be readily interchanged with interfollicular fibroblasts and used as an alternative cell source for establishing the dermal component of engineered skin both in vitro and in vivo.
生物工程皮肤构建体的生成方法是几十年前首创的;如今,这些构建体经常用于治疗严重烧伤和难以愈合的伤口。通常,这些构建体由胶原支架中的皮肤成纤维细胞组成,形成皮肤真皮,并在其上覆盖分层的角质形成细胞,形成皮肤表皮。在过去的十年中,人们对生物工程皮肤产生了浓厚的兴趣,研究人员正在寻找替代的细胞来源或支架,以便可以建立构建体,以及具有皮肤附属物的更仿生等效物。
评估人毛囊真皮细胞是否可以作为工程化皮肤构建体真皮成分的替代细胞来源。
我们通过将以下物质纳入胶原蛋白真皮室来建立体外皮肤构建体:(i)原发性毛囊间真皮成纤维细胞,(ii)毛囊真皮乳头细胞或(iii)毛囊真皮鞘细胞。通过将真皮细胞和角质形成细胞混合在免疫受损小鼠顶部的腔室中,建立体内皮肤。
所有成纤维细胞亚型都能够支持上皮细胞的生长,无论是在体外还是体内。然而,我们发现毛囊真皮鞘细胞在形成基底膜方面的能力优于成纤维细胞。
人毛囊真皮细胞可以很容易地与毛囊间成纤维细胞互换,并作为替代细胞来源,用于在体外和体内建立工程化皮肤的真皮成分。