Whether through injury or simple wear and tear, the skin’s integrity and function can be easily compromised. Although this impacts billions of people worldwide, little is known about how to prevent skin degeneration.
The Harvard Stem Cell Institute (HSCI) Skin Program is committed to understanding why skin sometimes fails to heal or forms scars, as well as why skin inevitably becomes thin, fragile, and wrinkled with age. The Skin Program’s ultimate goal is to identify new therapies for skin regeneration and rejuvenation.
How We Heal
Wound healing is a major problem for many older individuals. Furthermore, chronic, non-healing skin ulcers are a major source of health care costs and patient morbidity and mortality.
Human skin repairs itself slowly, via the formation of contractile scars which may cause dysfunction. In contrast, the axolotl salamander can readily regrow a severed limb, the spiny mouse has densely haired skin that heals with remarkable speed, and the skin of the growing human embryo can regenerate after trauma without the need for any scar formation. By studying these examples, scientists are finding clues for how to enhance skin healing through a more regenerative response.
Promoting Skin Regeneration
During normal wound healing, scars form from dermal cells that align in parallel. But when this alignment is disrupted by a biodegradable scaffold that directs cells to grow in a random orientation, the cells follow the diverse differentiation program necessary for true regeneration.
HSCI scientists have also identified biomarkers for the key cells involved in skin regeneration, and are developing therapeutic strategies for their enrichment and activation. Ongoing clinical trials are using skin stem cells to treat chronic, non-healing ulcers, and early results are promising.
Additional approaches include 3D bioprinting, where skin stem cells are layered into a complex structure that mimics skin and could be potentially used for transplantation.
Beyond Wound Healing
Skin aging can be thought of as a form of wounding, in which stem cells no longer maintain normal skin thickness, strength, function, and hair density. Understanding how to harness stem cells for scarless wound healing will also provide key insights into regenerating aged skin, a process termed rejuvenation. Multidisciplinary collaborators in the HSCI Skin Program are investigating the biological basis for how the skin ages over time and when exposed to ultraviolet radiation.
In addition to aging, skin stem cells also may mistake normal regions of the skin as wounds, then erroneously attempt to fill them. HSCI investigators are exploring whether this may be one of the underpinnings of psoriasis, a common and devastating disorder.
These areas of investigation are just the beginning. Skin stem cell biology has the potential to provide key insights into the mechanisms of regeneration for other organs in the body.