Tissue engineering of skin has come a long way in recent years, but it is struggling to progress from growing simple 2D sheets of tissue cells to regenerating a functioning, complex 3D organ complete with hair follicles, glands and connections to other organ systems.

Normal and iPS skinShare on Pinterest
The researchers made induced pluripotent stem (iPS) cells from mouse gum cells, and used them to grow complex skin tissue - complete with hair follicles and sebaceous glands - that functioned like normal tissue.
Image credit: RIKEN/Tsuji et al.

Now, a new study - by researchers in Japan and published in the journal Science Advances - appears to have made a significant step forward in skin bioengineering and regenerative medicine.

The skin is a complex organ that fulfills a number of functions. It is waterproof, provides cushioning, protects deeper tissues, excretes waste and regulates heat. For this to happen, a number of systems have to operate together within a complex 3D tissue architecture.

Study leader Dr. Takashi Tsuji, who heads an organ regeneration lab at the RIKEN Center for Developmental Biology (CDB) in Kobe, says:

"Up until now, artificial skin development has been hampered by the fact that the skin lacked the important organs, such as hair follicles and exocrine glands, which allow the skin to play its important role in regulation."

In their paper, the researchers describe how they made stem cells from mouse gum cells and used them to grow complex skin tissue - complete with hair follicles and sebaceous glands - in the lab.

Sebaceous glands secrete oily substances that help to keep the skin soft, smooth and waterproof. Together with hair follicles they form an important part of the "integumentary organ system" - the layer of complex tissue between the outer and inner skin.

In fully functioning skin, the integumentary system connects with other organ systems, such as nerves and muscle fibers.

The researchers implanted their 3D stem-cell generated skin tissues into living mice and showed that they formed these connections.

They believe their study is a significant step toward creating functional skin transplants for burn victims and other patients who require new skin.

The implants developed like normal skin

For the study, the team used chemicals to make the mouse gum cells regress into a stem cell-like state. Like embryonic stem cells, these so-called induced pluripotent stem (iPS) cells have the potential to differentiate into almost any other type of cell in the body.

When they grew them in culture, the researchers found the iPS cells developed correctly into what is known as an embryoid body (EB) - a 3D clump of cells that bears some similarities to a developing embryo.

The researchers implanted the EBs into mice with deliberately weakened immune systems. The EBs gradually differentiated into complex skin tissue - in much the same way as they do in a developing embryo.

Once the tissues had differentiated, the team then took them out of the first group of mice and transplanted them into the skin tissue of another group of mice. These implants developed normally as integumentary tissue.

The researchers also found that as the implanted tissue grew into integumentary tissue, it made normal connections with surrounding nerve and muscle tissues, allowing it to function normally.

The authors note that a key feature of their success was the use of Wnt10b signaling. This pathway is well known to be involved in controlling stem cells developing into fat tissue, bone, skin and other organs. They note how Wnt10b signaling led to a larger number of hair follicles, making the engineered tissue more like normal skin.

Dr. Tsuji concludes:

"We are coming ever closer to the dream of being able to recreate actual organs in the lab for transplantation, and also believe that tissue grown through this method could be used as an alternative to animal testing of chemicals."

Meanwhile, Medical News Today recently learned of another significant step forward for regenerative medicine in the form of a Chinese trial where children regrew new eye lenses following cataract surgery that removed diseased lenses but left the lens capsules and stem cells intact.