Skin Stem Cells and their Repair Mechanism

Skin is an essential tissue in our bodies. It protects us form infection and dehydration. It also allows us to feel different things like heat. So, our skin needs to be renewed continuously throughout our lives. For that it depends on different stem cells present in our body.

There are two main characteristic of stem cells. Firstly, they produce specialized cells and the second one is their self-renewal property. Usually, stem cells can be classified into embryonic stem cells and somatic stem cells. Embryonic stem cells are obtain from inner mass of blastocyst in mammalian embryos. These cells are pluripotent. Therefore, they have the ability to derive progeny cells belonging to all germ layers: ectoderm, endoderm and mesoderm. Whereas, somatic cells are usually found in mature organs or tissues. Some somatic stem cells could be multipotent but most of them exist as limited lineage. For example, hematopoietic stem cells can only give rise to mature blood stems and neural stem cells only divide into neuronal and glial cells.

With great achievement of Professor Yamanaka’s lab in Kyoto, differentiated, adult somatic stem cells can be reprogram to give rise to induced pluripotent stem cells (iPSCs). Currently, iPSCs have become new group of stem cells. The reprogramming is attain by adding four transcription factors (Oct-3/4, Sox2, c-Myc, and Klf4) using retroviral transduction. IPSCs can give rise to wide range of mature cell types and are pluripotent.

Skin stem cells fall in the category of somatic stem cells, but due to cellular heterogeneity of skin, there were many kinds of skin stem cells in past. Lately, with the help of molecular tools, many types of skin stem cells have been recognize. Different types of skin stem cells are:

Types of skin stem cells:

  • Epidermal Stem Cells:

These cells exist in the basal layer of epidermis. Two daughter cell are produce after every time stem cells divide. One has the characteristic of stem cells and other can derive into transient amplifying cells (TACs). The second one divides almost three to five time forming terminally differentiated cells (TDCs). Specified cell markers are p63, β1high/melanoma chondroitin sulfate proteoglycan + (MCSP+), α6high/CD71dim

  • Follicular Stem Cells:

They are found at the follicle bulge region. They can derive into hair follicle epithelium, including outer root sheath, inner root sheath and hair shaft. Specified cell markers are K15, CD34, Lgr5, Sox9, Lhx2, NFATC1, NFIB, K15.

  • Melanocyte Stem Cells:

These are located at the follical bulge region and hair germ. Melanocytes are melanin producing specialized cells that are responsible for skin, hair and eye pigmentation. Dct, Sox and Pax3 are the specifies cell markers.

  • Sebaceous gland Stem Cells:

Sebaceous gland stem cells located in sebaceous gland maintain its normal metabolism. They give rise to mature sebocytes, also can differentiate other cells such as involucrin positive cells. Blimp1 is unique cell marker.

  • Hematopoietic Stem Cells:

Found at the follical dermal papillae, they divide into erythroid and myeloid lineages. They share similar cell markers as counterparts in other tissue or organs.

Out of all these subgroups of skin stem cells, epidermal stem cells are the most correlated to tissue repair and skin regeneration. Research shows that stem cell of epidermis are rare, divide occasionally and make short-lived cells. Also, these short-lived cells are rapidly dividing to carry out regeneration of epidermis.

Repair Mechanism

Both epidermal and follicular stem cells contribute to the re-epithelialization of wounds after skin injury. According to study, epidermal stem cells reactive in response to skin injury and helps in skin regeneration on cellular level. Furthermore, clinical evidence suggest that epidermal stem cells and follicular stem cells play part in re-epithelialization of wounds by assessing the healing capacity of scalp follicle grafts transplanted into chronic leg ulcerations. Study showed that the size of ulcer areas decreased from 27.1% to 6.5%at the end of 18th week after the graft in ten patients. Also, Epithelialization, neovascularization, and dermal reorganization were build-up in these wound areas.

Hair follicular progenitor were mainly replaced by epidermal progeny after repair in long-term follow up. These findings might show that although epidermal stem cells and hair follicular stem cells combine in early phase of skin healing. However, hair follicle stem cells may not be needed for long term maintenance after skin repair.