Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications

Abstract

Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte stem cells (McSCs) residing in the epidermis of the skin. Many preceding studies have led to significant discoveries regarding the cellular and molecular characteristics of this unique stem cell population. The alteration of McSCs has been also implicated in several skin abnormalities and disease conditions. To date, our knowledge of McSCs largely comes from studying the stem cell niche of mouse hair follicles. Suggested by several anatomical differences between mouse and human skin, there could be distinct features associated with mouse and human McSCs as well as their niches in the skin. Recent advances in human pluripotent stem cell (hPSC) research have provided us with useful tools to potentially acquire a substantial amount of human McSCs and functional melanocytes for research and regenerative medicine applications. This review highlights recent studies and progress involved in understanding the development of cutaneous melanocytes and the regulation of McSCs.

Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization

“…Besides keratinocytes, multiple other skin cells have been shown to support optimal melanocyte function: for example, fibroblasts, adipocytes, endothelial cells, inflammatory cells, and dermal mast cells . All of these cell types potentially have a role in vitiligo repigmentation . In the following paragraphs, we will discuss repigmentation induced by UV light, which appears to be more complex and have superior stimulatory potential on melanocyte stem cells than other treatment alternatives.…”

Histochemical study of the distribution of epidermal melanoblasts and melanocytes in Asian human skin

“…Human melanocytes characterized by pigment‐producing organelles (melanosomes) and dendrites are located mainly in the epidermis and hair follicles of the skin. Melanocytes are derived from melanoblasts, undifferentiated precursors, which are originated from neural crest cells in early embryonic days . Differentiated melanocytes in the epidermis migrate into hair follicles and colonize hair bulb melanocytes where mature melanosomes are transferred to surrounding keratinocytes, and then, pigmented hairs are formed .…”

“…Melanocytes are derived from melanoblasts, undifferentiated precursors, which are originated from neural crest cells in early embryonic days . Differentiated melanocytes in the epidermis migrate into hair follicles and colonize hair bulb melanocytes where mature melanosomes are transferred to surrounding keratinocytes, and then, pigmented hairs are formed . Melanocyte differentiation requires many melanogenesis‐related proteins including tyrosinase (TYR), TYR‐related protein‐1 (TYRP1), dopachrome tautomerase (DCT or TYRP2), KIT, and microphthalmia‐associated transcription factor (MITF) .…”

“…Differentiated melanocytes in the epidermis migrate into hair follicles and colonize hair bulb melanocytes where mature melanosomes are transferred to surrounding keratinocytes, and then, pigmented hairs are formed . Melanocyte differentiation requires many melanogenesis‐related proteins including tyrosinase (TYR), TYR‐related protein‐1 (TYRP1), dopachrome tautomerase (DCT or TYRP2), KIT, and microphthalmia‐associated transcription factor (MITF) . In addition, the surrounding tissue environment, especially keratinocytes and fibroblasts, plays an important role in regulating melanocyte differentiation …”

Prospect of Human Pluripotent Stem Cell‐Derived Neural Crest Stem Cells in Clinical Application

“…Human melanocytes, which are primarily located in the hair follicles and skin, not only are essential for skin and hair pigmentation, but also protect the skin from ultraviolet irradiation [77]. It is notoriously known that the abnormal melanocytes are related to a wide range of severe diseases including vitiligo, albinism, and melanoma [78, 79].…”