Developing new tools for growing skin and hair ex vivo

开发体外生长皮肤和毛发的新工具

• 批准号: BB/H02431X/1
• 负责人: Carrie Ambler
• 金额: $ 15.33万
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH02431X%2F1
• 关键词: Developing; new; tools; growing; skin

Hair follicle development occurs only once in an animals' life during late fetal development and in newborns. In this short window of time all of the hair follicles within the body are generated. As healthy humans age some hair loss occurs in most adults, but additionally hair loss often accompanies scalp trauma either from physical wounding and burns or from chronic bacteria or fungal scalp infections. Hair loss is caused by irreversible changes to the hair-producing organ or follicle and renders it incapable of producing new hair. Hair plays a vital role in keeping animals warm, but importantly in today's society the contribution of hair to our physical appearance is tightly linked to the psychological well-being of humans. Hair loss, can cause anguish and negatively impact a person's self-esteem, self-image and confidence often leading to depression. Thus, not surprisingly billions of pounds are spent each year in the UK on hair loss solutions ranging from artificial hair implants to hair growth-stimulating chemicals to hair extensions and wigs. Considering the well-documented link between traumatic hair loss and poor mental health, one of the major efforts in skin research is to regenerate hair follicles in adult animals. However, before we can regenerate hair in adults it is imperative we understand how hair develops in an embryo. Yet, we have surprising gaps in knowledge about how normal hair forms. One contributing factor to these knowledge gaps is the lack of an appropriate technology to study the hair development outside of a living fetus. At present, hair follicles cannot be reconstituted from mouse or human cells grown in a laboratory. We can grow small pieces of mouse embryo skin in special growth media for a short period in the laboratory, but hair development stops in these conditions. Here in this grant, we propose a new technology to fill this void; a new method to study full and complete hair development outside of a living mouse fetus. We study hair and skin development in mice as it is unethical and impractical to study hair development in humans. Our proposed technology involves a 2-step process. Initially we will grow skin from early-stage mouse embryos before hair follicles start to form for a short time in the laboratory. During this period we can use techniques to alter the genes, cells and chemical pathways in this developing skin tissue. These alterations are not possible when the fetus develops inside the mother. Following this short growth period in the laboratory, we will re-implant these cultured skin tissues into a host chick or quail embryo to enable full skin and hair development. We will use chick or quail as hosts because we have shown that freshly-isolated mouse embryo skin develops hair follicles when directly implanted and grown in a bird (avian) embryo. This technology will provide us and the research community with a multi-use tool to study aspects of skin and hair development not possible using other techniques. We can determine the function genes of much faster than making new transgenic or gene knock-out mice, using significantly fewer research animals. This supports the BBSRC's commitment to reduce, refine, and replace animal usage. Additionally, we can track single skin cells during development and add additional cells into the developing skin. This will provide for the first time a method where cells modified in the laboratory can be rapidly tested in an appropriate and realistic model of hair development. Moreover, avian embryos are in self-contained shells that can be repeatedly opened and closed. Within this egg-shell, the growing skin and hair can be accessed making it possible to screen for drugs, growth factors and small molecules that impact hair development. In summary, this technology will aid our understanding of normal hair development and help us work towards our ultimate goal of safely re-growing hair in humans with extensive and traumatic hair loss.

在胎儿发育和新生儿期间，在动物的生活中，毛囊发育仅发生一次。在这个短时间的时间窗口中，体内所有毛囊均产生。随着健康的人类年龄，大多数成年人都会出现一些脱发，但是脱发通常伴随着头皮创伤，烧伤，烧伤或慢性细菌或真菌头皮感染。脱发是由产生发型器官或毛囊的不可逆转的变化引起的，并且使其无法产生新的头发。头发在保持动物温暖方面起着至关重要的作用，但重要的是，在当今社会中，头发对我们的外表的贡献与人类的心理健康紧密相关。脱发，可能导致痛苦，并对一个人的自尊，自我形象和信心产生负面影响，通常会导致抑郁症。因此，毫不奇怪的是，每年在英国花费数十亿英镑用于脱发解决方案，从人造植入物到头发生长刺激化学物质再到发胶和假发。考虑到创伤性脱发与精神健康不良之间有据可查的联系，皮肤研究的主要努力之一是再生成年动物的毛囊。但是，在我们可以在成年人中再生头发之前，必须了解头发在胚胎中的发展。然而，我们对正常头发的形成方式有惊人的差距。造成这些知识差距的一个促成因素是缺乏适当的技术来研究活胎儿以外的头发发育。目前，毛囊不能从实验室中生长的小鼠或人类细胞重构。在实验室的短时间内，我们可以在特殊的生长培养基中种植小鼠胚胎皮肤，但是在这些条件下，头发发育会停止。在这笔赠款中，我们提出了一项新技术来填补这一空白。一种研究活着的小鼠胎儿以外的完整和完整发育的新方法。我们研究小鼠的头发和皮肤发育，因为研究人类的头发发育是不道德和不切实际的。我们提出的技术涉及2步流程。最初，我们将从早期的小鼠胚胎中生长皮肤，然后在实验室短时间内毛囊开始形成。在此期间，我们可以使用技术改变这种发育中的皮肤组织中的基因，细胞和化学途径。当胎儿在母亲内部发展时，这些改变是不可能的。在实验室的短期生长期之后，我们将将这些培养的​​皮肤组织重新插入宿主的小鸡或鹌鹑胚胎中，以使皮肤和头发发育充分发育。我们将使用小鸡或鹌鹑作为宿主，因为我们已经表明，直接植入并生长在鸟类（鸟鸟）胚胎中时，新鲜分离的小鼠皮肤会发出毛囊。这项技术将为我们和研究社区提供一种多用途工具，可以使用其他技术研究皮肤和头发发育方面。我们可以使用更少的研究动物来确定比制造新的转基因或基因敲除小鼠的功能基因要快得多。这支持BBSRC减少，完善和替代动物使用的承诺。此外，我们可以在发育过程中跟踪单皮细胞，并在发育中的皮肤中添加其他细胞。这将首次提供一种方法，即可以在适当且现实的头发发育模型中快速测试实验室中修饰的细胞。此外，鸟类胚胎处于可以反复打开和关闭的独立外壳中。在这个蛋壳中，可以使用增长的皮肤和头发，从而可以筛选影响发育发育的药物，生长因子和小分子。总而言之，这项技术将有助于我们对正常的头发发育的理解，并帮助我们实现我们的最终目标，即在人类中安全地生长头发，并造成广泛而创伤性的脱发。

项目成果

Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

• DOI: 10.1371/journal.pone.0059811
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Wojciechowicz K;Gledhill K;Ambler CA;Manning CB;Jahoda CA
• 通讯作者: Jahoda CA

Modified methods for growing 3-D skin equivalents: an update.

用于生长 3D 皮肤等效物的修改方法：更新。

• DOI: 10.1007/7651_2013_47
• 发表时间: 2014
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Lamb R