Vitamin A’s key role in wound healing and stem cell biology

In the case of wounds or skin lesions, an active form of vitamin A regulates how stem cells initiate healing processes and produce new skin. This was demonstrated in a study from Rockefeller University that is published in the journal Science. In the future, researchers plan to look closer at how active vitamin A can be used to regulate stem cells as a way of preventing and treating skin cancer.

The outer skin layer (epidermis) contains stem cells that gradually develop the other protective skin layers within a period of a month. If you fall and scrape your knee or elbow against the ground, the body immediately begins a healing process to seal off the injured skin and repair the damaged epidermis. Some of the stem cells from the epidermis enter the sore to support the healing process. Previous stem cells from hair follicles that are normally responsible for hair growth, also participate in the healing process. In order to do this, however, the hair follicle stem cells have to enter a special development phase through a process known as linear plasticity.
The team of scientists from Rockefeller University found that the biologically active form of vitamin A known as retinoic acid plays a key role in the linear plasticity and development of stem cells in connection with healing processes.

Wound healing and cell division must be controlled

Earlier studies have looked at linear plasticity as a natural response to wound healing, and it is particularly easy to study this phenomenon in skin injuries. Scientists have found that stem cells from hair follicles are the first to participate in the healing process.
When the scientists from Rockefeller University looked closer at the processes, they found that linear plasticity can be both beneficial and harmful. As mentioned earlier, linear plasticity is useful for wound healing, but if the process is not carefully regulated, the cell division risks spinning out control so different cancer forms can develop.
To get a better understanding of how linear plasticity works, the researchers studied hair follicle stem cells from mice under conditions that resembled a wound healing process. They were surprised to see that retinoic acid played such a crucial role in helping the stem cells carry out linear plasticity correctly.
It is commonly known that vitamin A contributes to skin health, and the researchers conducted both in vitro- and in vivo-studies to see how the vitamin affected wound healing. Diet and genetic factors can also affect the body’s ability to utilize vitamin A and influence how stem cells initiate healing processes and hair growth.
In addition, the active form of vitamin A collaborates with other molecules such as BMP (bone morphogenetic protein) and WNT (wingless-related integration site). This affects whether stem cells remain inactive or participate actively in wound healing and hair growth.
Still, vitamin A therapy has shown conflicting results. Treatment with retinoic acid can stimulate new hair growth in connection with wound healing, whereas too much retinoic acid can cause alopecia. In the future, researchers therefore want to look closer at how much vitamin A we need to help stem cells and wound healing function optimally. Also, they want to see how vitamin A affects other tissues.

Vitamin A from food and in its active form

In animal foods like butter, egg yolks, and oily fish, vitamin A occurs as retinol, which is considered pure vitamin A. Vegetable sources like carrots and spinach contain beta-carotene, a vitamin A precursor that is converted into retinol in the body. Retinol is stored in the liver. Our skin and many other tissues receive retinol and convert it into retinoic acid, which is needed for stem cells and their linear plasticity and for wound healing.

Cancer and regulation of linear plasticity

In the future, scientists also want to see how active vitamin A affects linear plasticity in connection with cancer, especially basal cell carcinoma and squamous cell cancer.
Cancer stem cells are derailed. According to the scientists, this may be a result of errors in the coding of the stem cells’ linear plasticity.
In basal cell carcinoma, which is far less aggressive than squamous cell cancer, the linear plasticity is relatively limited. The researchers therefore see a therapeutic potential if future studies demonstrate that retinoic acid can help inhibit linear plasticity. This process may be a key factor in the battle against cancer cells. Also, inhibiting linear plasticity may improve the prognosis.

References:

Matthew T. Tierny et al. Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices. Science, 2024

Rockefeller University. Vitamin A may play a central role in stem cell biology and wound repair. ScienceDaily 2024

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