The field of biomedical engineering has made great strides in recent decades, with scientists now able to develop artificial muscles, regenerated thymus gland and even microscopic cardiac tissues that are capable of beating like a real heart. For the very first time, a team of Japanese researchers has grown complex skin tissue, containing hair follicles as well as sweat glands, in the laboratory. The breakthrough, the group believes, could help treat burn victims and other patients in need of skin transplants.
Although epithelial cells have been artificially grown as implantable sheets in the past, they have largely remained rudimentary in their form and function. The new research, according to the scientists, marks the first time that functional skin tissues, possessing sebaceous glands and hair follicles, have been created in the laboratory. The study was conducted by Japan-based RIKEN Center for Developmental Biology (CDB), in collaboration with researchers from the Tokyo University of Science and other regional institutions.
Recently published in the Science Advances journal, the research outlines the technique adopted by the team to develop lab-grown skin that closely approximates the characteristics of normal tissue. For the project, the group first obtained cells from the gums of mice, using specific chemicals to convert them into induced pluripotent stem cells (iPSCs). Known for their role in regenerative medicine, these undifferentiated cells are capable of propagating indefinitely and also developing into all other types of cells present in the human body.
When exposed to Wnt10b signaling and implanted into a bunch of immune-deficient mice, the iPS cells underwent a transformation, turning into a three-dimensional cellular structure called embryoid body (EB). At this stage, the cells were transplanted onto healthy, hairless mice, where they gradually differentiated into what is known as integumentary tissue, i.e. this type of tissue found between the outer and the inner layers of skin and responsible for a variety of tasks, including fat excretion and hair shaft eruption.
To create artificial cells that replicate the functionality of real skin, the scientists grew multiple batches of tissues that resembles different parts of skin, such as dermis, epidermis and the subcutaneous fat layer. According to the team, the lab-grown cells featured a set of working sweat and oil-secreting glands, as well as hair follicles. What is more, they exhibited the ability to make normal connections with surrounding muscle fibers and nerves.
As the researchers point out, the success of the technique was largely dependent on Wnt10b signaling, which in turn facilitated the production of hair follicles, thus creating a bioengineered tissue that is strikingly similar to real skin. One of the major problems currently faced by the team pertains to the fact that although these newly-developed cells can connect to nerve fibers, they are incapable of actually making them.
This drawback, the scientists believe, could be an issue in case of patients with extreme nerve damage. Furthermore, the group has found that the hair growing on the artificially-generated tissue is at times very different from that appearing on the rest of the body. For instance, one white-furred mouse had thick, black hair growing from the artificial skin. It might be another ten years before the technology is ready for use in clinical settings. Speaking about the research, Takashi Tsuji, a member of the team, said:
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. With this new technique, we have successfully grown skin that replicates the function of normal tissue. 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.