Biomaterial approaches for cell-based therapies

Abstract

Cell-based therapy is a method to treat diseases by introducing new cells into an injured organ. The approach has been investigated for treatment of a range of ailments, including myocardial infarction. Therapeutic cells can be introduced in several ways, including the direct injection of exogenous cells and the injection of chemoattractant molecules that recruit endogenous cells. In the case of treating cardiovascular diseases, clinical studies in patients have shown that these cell-based therapies are generally safe, but have yet to show substantial efficacy in improving heart function. A major hurdle facing the translation of cell therapy from the laboratory to the patient is that it is difficult to maintain a sufficient number of the therapeutic cells at the site into which they are recruited or injected. The work described in this dissertation, therefore, focused on biomaterial-based approaches to address the problems of poor recruitment, attachment, and retention of transplanted cells. First, biodegradable polymer microspheres were developed to release a chemoattractant molecule, SDF-1 alpha, in a sustained manner and resulted in the successful recruitment of stem cells in vitro. Second, charged polymers were deposited onto cell surfaces and successfully demonstrated that the coatings modified the attachment of cells to surfaces. Lastly, two different types of hyaluronic acid-based hydrogels were developed that may be used to immobilize cells in a depot and improve cell retention at the site of injection: an environmentally-responsive chemically crosslinked hydrogel that gels based on in vivo physiology, and a physically crosslinked hydrogel that undergoes shear reversible gelation. The results of this body of work demonstrate in model systems the types of strategies that can be used to create biomaterials for cell-based therapies. These approaches may be implemented in the future to improve the clinical outcomes of these therapies.