Stem cells and repigmentation in vitiligo
Cellular messaging: receptors, ligands and signaling pathways
Each cell within the body has one or more receptors; molecules on or within the cell to which other molecules, called ligands (such as peptides), bind. This binding causes changes within the cell which normally follow set ‘signaling’ pathways. Signaling pathways are responsible for cellular responses, allowing other cells and external elements to alter how a cell functions. There are two types of ligands which bind to receptors: agonists, which then promote a response in the pathway, and antagonists, which lead to an alternate response.
Much of modern drug development is based on a simple concept: whether a pharmaceutical, when correctly administered, can activate or inhibit a pathway within cells to achieve a therapeutic benefit.
The skin and its pigment producing cells
The skin is the largest organ in the human body and is exceedingly complex. Multiple cells and layers which comprise the skin serve different functions to help protect and regulate the body. By viewing a cross-section of the top layers of the skin (the epidermis and dermis, see Figure 1), one can gain an understanding of how the interactions between skin cells and environmental factors affect the skin. While the complete function of the skin is discussed in greater depth on our website, a brief overview is necessary here.
Epidermal melanocytes, cells which produce pigment in the skin, lie at the base of the epidermis, while keratinocytes – both squamous cells and basal cells – make up the majority of the top layer of the skin. The ratio of melanocytes to keratinocytes in healthy skin is 1:36. Keratinocytes turn over quickly in the skin, migrating from the base to the top of the epidermis as they age and ‘sloughing off’ at the surface; generally this turnover takes 28 days in healthy adults. Melanocytes, by contrast, live for many years but are significantly less able to multiple and renew themselves compared with keratinocytes.
Melanocytes also exist at the root of the hair follicle, in the matrix of the inner root sheath or shaft, and are responsible for giving the hair its colour. The dermis, the layer of the skin beneath the epidermis, consists mostly of collagen, elastic tissue and reticulum fibres, along with some specialised nerves and glands. The base of the hair follicle is also embedded in this layer. Part of the outer root sheath of the hair follicle forms a bulge, a region called the ‘niche’. Contained within the niche are partially differentiated stem cells: immature cells which, given the right conditions, can be activated to develop into several cell types.
Vitiligo is a skin disorder in which the melanocytes within the basal layer of the skin are damaged or completely destroyed. It is this loss of melanocyte function that causes depigmentation of the skin, which generally occurs in patches or ‘lesions’.
Signaling pathways in the melanocyte
There are four significant signaling pathways that affect melanocyte function within the skin. Each pathway involves a receptor – READ MORE FROM ORIGINAL SOURCE