Further Progress in Tissue Engineering of Skin

Over the past decade, promising inroads have been made in the production of "good enough" engineered skin tissue, and it has advanced to the point at which production methodologies can be automated, building skin from a patient's own cells. The varied forms of tissue generated by these approaches differ from natural skin in many ways: they do not have the same layering of specialized cell types, and lack blood vessel networks and other features of skin such as hair follicles, sweat glands, and lymphatic systems. Still, they can successfully replace lost skin and integrate with a recipient patient's tissues. This represents a big improvement in the quality of treatment and the prognosis for burn victims and other patients who have lost large sections of skin.

As is usually the case, the technologies at the end of the research pipeline closest to realization are considerably less advanced than the work still in progress in the laboratory. We live in an age of rapid progress, and the newly launched technology is already heading towards obsolescence. Even as forms of first generation tissue engineered pseudo-skin become available as an option for hospitals and clinics, the research community is closing in on the production of much more natural and fully-featured skin, again produced from a patient's own cells. Once realized and deployed, this will represent another leap ahead for the treatment of injured and lost skin. In the publication and publicity materials noted here, researchers report on achieving the goal of complex, more fully featured skin in mice:

This Lab-Grown Skin Grows Hair and Can Sweat

Scientists have developed a new method to grow 3D layers of skin and hair cells from stem cells - which are genetically engineered from adult tissue. The scientists' lab-grown skin includes all three layers of skin cells, as well as sweat glands, hair follicles, and your skin's oil-producing glands called sebaceous glands. That's far and away more complex than the next best attempt to artificially regenerate skin, which only includes two types of skin cells. To test their new skin, the researchers took a DNA sample from an adult nude mouse, built a chunk of skin with it, and successfully implanted skin back in the mouse, where it thrived and grew hair. The skin and hair prospered over the entire 70 day period it was meant to last.

To build their multi-layered suite of skin cells, the researchers first collect a small sample of adult tissue. This can be as simple as taking a drop of blood. Although, for their mice, the team scrapes away a tiny bit of mouse's gums. The scientists are then able to genetically engineer those adult cells to revert into stem cells that share the donor's DNA, called induced pluripotent stem cells, or iPS cells. The team found a way to nurture those iPS cells to generate into a package of skin and hair cells. This is done by growing the stem cells in en environment infused with the right combination of chemical signals. This tricks the iPS cells into thinking they need to start forming skin, which can then be harvested in chucks containing between one and two dozen hair follicles. Using this same adult-derived stem cell process, the researchers are also now looking at ways to regenerate various parts of your mouth, including teeth and salivary glands.

Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model

The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. The integumentary organs include the skin and its appendages (hair, sebaceous glands, sweat glands, feathers, and nails). We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bioengineered 3D integumentary organ system was fully functional following transplantation into nude mice and could be properly connected to surrounding host tissues, such as the epidermis, arrector pili muscles, and nerve fibers, without tumorigenesis. The bioengineered hair follicles in the 3D integumentary organ system also showed proper hair eruption and hair cycles, including the rearrangement of follicular stem cells and their niches.

No April Fool's today?

Posted by: Patrick Colleton at April 1st, 2016 8:16 PM

While this is great news, I'm inclined to think that the focus on incorporating hair is a misaligned priority. I mean, for most of the skin area on the human body the hair is considered superfluous or even an aesthetic defect. On the other hand, hair follicles are connected to glandular systems within the skin, so perhaps this justifies it as part of a holistic approach to replicating all the relevant biological systems.

Posted by: José at April 6th, 2016 4:17 AM

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