Early Translational I
ICOC Funds Committed:
Medical care for burn patients has advanced in the last few decades. This is due, in large part, to medical research that has contributed to the management of fluid loss and infection. Now, morbidity rather than mortality is the main issue in burn care. Technology has advanced so we can save lives by replacing damaged or missing skin with skin autografting or dermal equivalent products made from animal products. However, grafted skin is unable to completely restore normal skin function. For skin to function normally, it requires multiple skin appendage organs. These include hair, sebaceous gland, etc. Sebaceous glands are necessary for normal skin lubrication and patient without glands will have lifelong requirement for daily moisturizer to replace skin oils. Hair functions in direct relationship to external appearance which directly influences a patient’s quality of life. We have recently developed a new method of growing hair from newborn mouse skin cells. The cells can organize themselves and form skin which contains normal hairs distributed in a cosmetically acceptable fashion. We will also apply the concept of improving the "macro-environmental regulation of hair stem cell activity", based on a paper we just published in Nature this January. By preparing the soil to be more fertile, we increase the success of stem cell regeneration. Together these represent major advances in skin appendage regeneration. Here we propose to bring this progress from basic research to the pre-clinical research phase, so that the technology can be ready for clinical trials at the end of the 3 year funding period. This work offers another significant step in the saga of stem cell engineering. As of today, bone marrow stem cells have already been in clinical use because no spatial organization is needed. However, for many organs, tissue architecture is essential for function. While scientists can exert some control over the stem cell differentiation, our inability to turn a population of stem cells into topologically-organized tissues becomes a bottleneck preventing their use in therapy. The success of this work will be the first in this category of stem cell engineering. One of the major concerns in the use of stem cells is their potential to form tumors. Therefore there is a great need to develop imaging methods that can track stem cells once they are in the body, so one can detect any early changes. Since the skin is on the surface, we can verify that the cells contribute to appropriate skin structure, and biopsy can be done easier to verify changes in radiological imaging. Principles learned this way can also be applied to the stem cell research of other organs. The ability to reconstruct skin appendages has profound implications to benefit patients. In addition to burn patients, there are numerous congenital, post-traumatic and acquired deficiencies of hair. Success would allow clinicians to treat these patients as well.
Statement of Benefit to California:
The recent firestorms in southern California remind us of the dangers from natural disasters in our environment. An article published in the Insurance Journal, May 2008, estimates that a 7.8 magnitude earthquake could cause over $87 billion worth of damage from fires ignited by ruptured gas lines and other sources. Currently, over 100,000 patients are treated for burn injury in the United States per year. In the event of a catastrophe such as wildfire, earthquake or even terrorist attack, that number could skyrocket beyond what medical practitioners can handle. Burns can cause lasting appearance and functional defects to visible areas on the skin. Research has taken today’s burn care beyond just keeping the patient alive and fighting against infection and fluid loss. Appearance can profoundly affect one’s physical and psychological well-being, especially when altered after a severe disfiguring injury. Current technology has improved the mortality rate of burns tremendously, but improvement of the morbidity rate of burn injuries has a long way to go. Our goal is to create normal skin for burn victims. Currently, burn victims have scars, which never look or feel like normal skin. The main difference between scar and normal skin lies in the fact that scar does not have hair, sweat glands, or oil glands. While we may find these to be ancillary, lack of any or all of these causes significant suffering in a patient with scars. Evolutionarily, hair kept people warm. Today, billions of dollars are spent nationwide in the grooming and restoration of hair. It is conceivable that the benefit of our ability to use stem cells to grow hairs can be extended beyond restoration of normal skin architecture. The current gold standard of treatment for hair loss is hair transplantation, which is a laborious and expensive procedure. Essentially, a strip of hair bearing skin is surgically taken from the patient. The individual hair follicles are then painstakingly dissected out one by one and planted into small slits are made on the recipient’s skin. Patients who do not have enough hair as a result of previous injury (such as burn), cannot spare extra hair to transplant. There is just no way to increase the total number of hairs. In contrast, our stem cell based hair growth can generate many more new hairs from the stem cell pool. We seek to generate completely new hairs from a patient’s own stem cells, although we also will pursue other strategies. The hair will be permanent and will look and behave like natural hair. Hair restoration has profound implications for both the medical field and the cosmetic industry. The ability to harness stem cells toward forming normal looking, hair-containing skin has a huge potential market. The people of California not only will benefit from having new therapeutic treatment for hair restoration following traumatic injury, but also can reap financial benefit from their stake in supporting the development of this technology.