Protein-Based Hydrogels for Cell Transplantation under Constant Physiological Conditions
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1060-LL09-04
Protein-Based Hydrogels for Cell Transplantation under Constant Physiological Conditions Cheryl T Wong Po Foo1, and Sarah Heilshorn2 1 Materials Science and Engineering, Stanford University, 476 Lomita Mall, Mc Cullough Bldg Rm 222, Stanford, CA, 94306 2 Materials Science and Engineering, Stanford University, 476 Lomita Mall, McCullough Building, Room 246, Stanford, CA, 94305-4045 ABSTRACT A promising treatment for multiple neurological disorders including stroke, Huntington's, and Parkinson's is the transplantation of stem cells into the diseased site to promote regeneration of the neural tissue. However, viability of transplanted cells is often low (15-35%) and unpredictable[1-3]. Cell viability has been directly correlated with functional outcome of the treatment[4, 5], motivating the development of more reliable cell transplantation procedures. To protect transplanted cells from shear stress during injection and from the hostile, inflammatory environment of the diseased brain tissue, we have designed a two-component, protein-based hydrogel system that can self-assemble under constant physiological conditions. The first hydrogel component is a block copolymer made of several repeats of a peptide sequence encoding the WW domain-fold, a short triple-stranded, anti-parallel beta-sheet. The WW domains are interspersed with a random-coil, hydrophilic spacer to enhance polymer flexibility and solubility. The second hydrogel component is made of several repeats of a polyproline rich peptide sequence interspersed with a random-coil, hydrophilic spacer. Upon mixing the two hydrogel components together, the WW-domains in component 1 and the polyproline rich peptides in component 2 bind together with 1:1 stoichiometry. This binding has an apparent association constant of 2.5x105 M, as measured by isothermal titration calorimetry. This peptidebinding event serves as the physical crosslinks to form a polymeric network composed of the two components. Because gelation is initiated by simply mixing the two components together at constant physiological pH, temperature, and ionic strength, this system is highly biocompatible and easy to use. Furthermore, the precision of protein engineering allows both components to be easily modified. INTRODUCTION The adult central nervous system, unlike other tissues, has a limited capacity for selfrepair, and endogenous neural stem cells are restricted in their ability to generate new functional neurons in response to injury or disease. As a result, neural stem cell transplantation directed to the injured or diseased sites has emerged as a promising treatment for multiple neurological disorders including stroke, Huntington's, and Parkinson's to promote regeneration of the neural tissue. Although a variety of transplanted neural progenitor cells and stem cells have had some degree of success in improving functional recovery, cell survival after transplantation in animal models is often poor and unpredictable[1-3], and has been directly correlated with functional outcome of the trea
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