Tunable hydrogels for therapeutic delivery of multipotent stem cells.
Rationale: Skin ulcers represent the largest economic burden of all skin diseases. Human adult stem cell therapies for the treatment of chronic wounds have shown considerable promise. However, a delivery system is needed before they can be used clinically. Hydrogels have emerged as a promising vehicle for stem cell delivery because their 3-D structure and high water content mimic the natural environment of the stem cell. However, the surface of some hydrogels cannot interact well with stem cells. Our objective is to develop hydrogels with small adhesion contact sites for stem cells to allow the stem cells to interact better with the hydrogels. We will also make hydrogels with other biomolecules to better promote wound healing. If successful this research will lead to new therapies for chronic wounds.
Diseases of the skin are among the medical conditions in which spending has increased the most. Within this group, skin ulcers represent the largest economic burden. In 2004, the prevalence of skin ulcers was 4.8 million, far below the prevalence of other common skin diseases. However, the total healthcare cost for these patients, not including intangible cost due to quality of life impact, was $11.951 billion. This is five times higher than the economic burden of non-melanoma skin cancer, the most prevalent cancer in the U.S.. Current treatment options for patients with ulcers are limited and often ineffective. Even with the best care, the healing rate is only between 30-70% at 6 months and the recurrence rate is >70%. Ulcers are also a major risk factor for amputation, especially in patients with diabetes. This is true for people of any state, including California. Human adult stem cell therapies for the treatment of chronic wounds have shown considerable promise. However, their clinical application is predicated on developing an appropriate delivery platform, and relatively little research has been conducted in this area with respect to cutaneous wound healing. This proposal outlines an approach to develop novel stem cell delivery platforms. If successful this will lead to new treatments for chronic wounds.
Human adult stem cell therapies for the treatment of chronic wounds have shown considerable promise. However, appropriate delivery systems are needed to apply these therapies in the clinic. This award funds the development of stem cell delivery systems for the treatment of chronic wounds. We envisioned that tunable hydrogels can be used to deliver stem cells to wounds. Over the past year we have been engineering hydrogels for this application. First, we screened large libraries of small molecules and identified a variety of stem cell-specific small molecules. These molecules have the ability to bind to stem cells. So far we have demonstrated that the small molecules can capture stem cells on 2-D surfaces. In the upcoming years we will determine their ability to hold stem cells within hydrogels. We expect that the different small molecules will have different effects on the stem cells. So we will also test for this. In addition, we have developed a variety of hydrogels that degrade at different rates. We have demonstrated that these hydrogels can polymerize within a living organism and that their degredation rate can be set by their building blocks. In the upcoming year(s) we will attach our stem cell-specific small molecules to our hydrogels and then use these hydrogels to treat chronic wounds.
Integrins are cell surface receptors that allow cells, including stem cells, to interact with their environment. One of their functions is to transmit signals about the environment to stem cells. There are many types of integrins, which bind to extracellular proteins found in a cell's environment. Our group has been using chemistry to isolate different novel small molecules that can bind specifically to the different integrins. Our goal is to incorporate these novel small molecules into hydrogels, which we are using as 3 dimensional homes to grow stem cells within the incubator. The ultimate plan is to use these same hydrogels to transfer the stem cells to patients with a variety of ailments, such as chronic ulcers.
Over the past year we have helped to develop a variety of hydrogels that can grow stem cells. We have also isolated a variety of novel small molecules specific to different integrin molecules.