Epidermal stem cells have been used in treatment of burns and skin ulcers for decades in the basic form of skin grafts. Recent, technology has provided modern ways of treatment these two conditions.
The epidermis is the outer layer of the skin. This part of skin is unique because it constantly renews itself. Epidermis is made of keratinocytes mostly, but also of Langerhans cells, melanocytes and Merkel cells. In normal skin loss and traumatic skin loss like burns and skin ulcers epidermal stem cells are responsible for epidermal ability of regeneration.
Nowadays burns and skin ulcers are very common injuries. Despite their frequency, both of these injuries are very expensive for treatment because of slow-rates of healing and possible complications.
Epidermal Stem Cells
Epidermal stem cells are founded in basal layer of the skin. Epidermal stem cells produce mature functional supra basal keratinocytes. These cells are responsible for self-maintenance and self-renewal. If there is a need for extra basal cells they are able to divide themselves in several number of times in order to produce more mature functional keratinocytes.
Standard skin grafts
Skin grafting is skin transplantation to the open wound and it is used to provide coverage for wounded area. Skin grafts can be classified in autologous, allogeneic, xenogeneic and prosthetic skin grafts. In some classifications, we can find Isogeneic (transplatation between twins). Also, grafts can be classified by thickness in full-thickness grafts, split thickness grafts (these grafts are grafts with epidermis and part of the dermis) and composite grafts.
Current Use of Stem Cells in Burn Treatment
Epidermal cells can be modified both in vivo and ex vivo by viral and non-viral methods. In the first experiments with skin stem cells scientists tried to eliminate inherited genetic defects, but now these cells are used in wound healing therapy with genetically modified keratinocytes and growth factors.
The basic concept of burns treatment with stem cells is growing them on some scaffold, and then transfer to patients wound. Replacing of the skin grafts with stem cell cultures is main goal of this method. Faster healing rates and compatibility with recipient's immune system are big achievements of stem cell technique.
Main parts of stem cell production are somatic cells and egg cell. DNA from the somatic cell have to be evacuated from the somatic cell, and the rest of the cell can be discarded. Also, DNA of the egg cell is extracted and discarded. Then somatic DNA is inserted into an egg cell. The egg cell influences and reprograms the DNA from the somatic cell. This so-called embryonic cell can be induced to differentiate into skin keratinocyte under specific laboratory conditions and can be used for generating artificial skin. This is the way of creating unlimited amounts of graftable skin.
In mid-1970s, a technique for serial cultivation of epidermal cells, producing the 1000- to 10000-fold area of graftable epidermis was developed. This skin grafts were very sensitive to bacterial infection, and they can be placed directly on muscle or fascia. The only problem with this technique are expenses.
Skin has great regenerating potential. Epidermis has adult stem cells which are classified in groups on the basis of their regenerating power in: holoclone keratinocytes, paraclone keratinocytes and meroclone keratinocytes. Holoclone keratinocytes are the most important cells in this classification.
Holoclone keratinocytes are skin adult stem cells with biggest dividing potential (over 140 divisions). Only holoclone keratinocytes can be growth in vitro in addition of growth factors. Autologous holoclone keratinocytes can create full thickness skin and they can be used in treatment of massive burns. Holoclone keratinocytes grafted on damaged skin proliferate effectively and they promote healing of the burns. Lack of this method is that holoclone keratinocytes are not so efficient at deeper burns. Basic problem with this method is lack of dermal layer which supports keratinocytes layer. Thus, holoclone keratinocytes are grown on substrates. Substrates for this method must have collagen gels and cryopreserved dermis.
Fetal skin cells in grafts
This therapy method includes fetal skin cells from aborted fetuses. Fetal cells are very potent cells for regeneration. This tissue is used for patients with deeper burns, and it was imagined that this tissue is some kind of biological bandage. During the research, scientist have discovered that fetal tissue promotes growth of the patient's own skin.
This procedure starts with separation of fetal cells from the skin of aborted fetuses. Aborted fetuses skin cells divide in vitro. Then, the skin cells are allowed to grow on substrate of collagen. This procedure is used to get more than million 100cm2 grafts from a single biopsy.
The patches obtained in this way were used in burn treatments, and they have not shown any complications. It took 15 days to heal the wound. There were no retraction of the skin, and not a single one rejection of the patch. Patients grafted skin was considered as almost perfect. There was a question after this method success. What happened with fetal skin stem cells? This question remains unanswered, but one thing was sure- these grafts were better than true skin grafts.
Human umbilical cord blood stem cells
These cells have property to differentiate into epithelial cells in vitro under specific conditions. This property of human umbilical cord blood stem cells is also considered as possible solution for skin-grafting.
Also, hemopoietic stem cells transplanted on the burn sites can decrease healing time.
Standard skin grafts are very good solution for extensive burns, and it will be in nearly future basic and only solution in many parts of the world. However, considering advantages of skin stem cell tissue engineering, it is clear that this method will be the future of transplantation. The only disadvantages of this method are currently development and big expenses of tissue production.