California's Stem Cell Agency

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.

During this funding period we have identified many molecules that can bind to stem cells. When stem cells are cultured with these cells, we have found that some of the molecules induce the stem cells to differentiate while others induce them to proliferate but not differentiate. We will continue to characterize these ligands. We have also dramatically improved our methodologies to identify new stem cell-binding molecules. We are now incorporating stem cell-binding small molecules into hydrogels to characterize the effects of these ligands on stem cells in a 3D culture system. We have also demonstrated that several parameters of the 3D hydrogel cultures can be “tuned” to achieve optimal results, i.e. controlled stem cell differentiation. In addition, to our extensive experimentation with cultured stem cells, we have started to characterize the properties of our hydrogels when implanted into an animal model, and have been able to control the degradation rates within the animals. Those results demonstrated that we can “tune” hydrogels to degrade at different rates. This technology can be incorporated into a variety of Stem Cell applications. We have also started to incorporating stem cell-binding molecules into hydrogels and have tested their ability to increase the rate of wound healing. From these experiments, it appears that our functionalized hydrogels containing our synthetic molecules are able to increase the rate of wound healing. Another fascinating finding is that our stem cell-binding small molecules appear to be able to alter the differentiation of mesenchymal stem cells when they are incorporated into 3D cultures.