Research into bioengineering has led to important achievements in recent years, with a number of different tissue types being developed. In the area of skin tissue epithelial cells have been successfully grown into implantable sheets, however, they do not have the proper appendages, the oil-secreting and sweat glands, that would allow them to function as normal tissue. Now, researchers led by the RIKEN Center for Developmental Biology (CDB) have successfully grown complex skin tissue, complete with hair follicles and sebaceous glands, in the laboratory; they were then able to implant these three-dimensional tissues into living mice, and the tissues formed proper connections with other organ systems such as nerves and muscle fibers. The team state that this work opens a path to creating functional skin transplants for burn and other patients who require new skin. The opensource study is published in the journal Science Advances.
Previous studies show that the integumentary system is an organ system consisting of the skin, hair, nails, and exocrine glands that protects the body from various kinds of damage. The integumentary organs arise from organ germs through reciprocal epithelial-mesenchymal interactions in the skin field. During embryogenesis, the skin field forms through a regulated process of pattern formation, and its appendage organs are then induced through epithelial-mesenchymal interactions. Regeneration of integumentary organs using 3D stem cell culture could contribute to regenerative therapies for patients with burns, scars, and alopecia, and could be used as a novel assay system for non-animal safety testing of cosmetics and quasi-drugs. However, it is difficult to generate the complex integumentary organs and to replicate the physiological functions of the skin using in vitro stem cell culture or in vivo transplantation models. The current study generated integumentary organs from iPS cells, which includes functional appendages such as hair follicles and sebaceous glands.
The current study harvested cells from mouse gums and used chemicals to transform them into stem cell-like iPS cells. Results show that in culture, the cells properly developed into what is called an embryoid body (EB), a three-dimensional clump of cells that partially resembles the developing embryo in an actual body. Data findings show that EBs developed from iPS cells using Wnt10b signaling, and that treatment with Wnt10b resulted in a larger number of hair follicles, making the bioengineered tissue closer to natural tissue.
Multiple EBs were then implanted into immune-deficient mice, where they gradually changed into differentiated tissue, following the pattern of an actual embryo. Once the tissue had differentiated, the lab transplanted them into the skin tissue of extraneous mice, where the implants developed normally into the tissue between the outer and inner skin that is responsible for much of the function of the skin in terms of hair shaft eruption and fat excretion. The group note that they also found that the implanted tissues made normal connections with the surrounding nerve and muscle tissues, allowing it to function normally.
The team surmise that with their new technique they have successfully grown skin that replicates the function of normal tissue. For the future, the researchers state that they 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.