pH-sensitive and thermosensitive hydrogels as stem-cell carriers for cardiac therapy.pdf

2019-03-04T23:52:21Z (GMT) by Jianjun Guan Zhenqing Li
<div>Stem-cell therapy has the potential to regenerate</div><div>damaged heart tissue after a heart attack. Injectable hydrogels may be</div><div>used as stem-cell carriers to improve cell retention in the heart tissue.</div><div>However, current hydrogels are not ideal to serve as cell carriers because</div><div>most of them block blood vessels after solidification. In addition, these</div><div>hydrogels have a relatively slow gelation rate (typically >60 s), which</div><div>does not allow them to quickly solidify upon injection, so as to</div><div>efficiently hold cells in the heart tissue. As a result, the hydrogels and</div><div>cells are squeezed out of the tissue, leading to low cell retention. To</div><div>address these issues, we have developed hydrogels that can quickly</div><div>solidify at the pH of an infarcted heart (6−7) at 37 °C but cannot</div><div>solidify at the pH of blood (7.4) at 37 °C. These hydrogels are also</div><div>clinically attractive because they can be injected through catheters</div><div>commonly used for minimally invasive surgeries. The hydrogels were</div><div>synthesized by free-radical polymerization of N-isopropylacrylamide, propylacrylic acid, hydroxyethyl methacrylate-cooligo(</div><div>trimethylene carbonate), and methacrylate poly(ethylene oxide) methoxy ester. Hydrogel solutions were injectable</div><div>through 0.2-mm-diameter catheters at pH 8.0 at 37 °C, and they can quickly form solid gels under pH 6.5 at 37 °C. All of the</div><div>hydrogels showed pH-dependent degradation and mechanical properties with less mass loss and greater complex shear modulus</div><div>at pH 6.5 than at pH 7.4. When cardiosphere-derived cells (CDCs) were encapsulated in the hydrogels, the cells were able to</div><div>survive during a 7-day culture period. The surviving cells were differentiated into cardiac cells, as evidenced by the expression of</div><div>cardiac markers at both the gene and protein levels, such as cardiac troponin T, myosin heavy chain α, calcium channel</div><div>CACNA1c, cardiac troponin I, and connexin 43. The gel integrity was found to largely affect CDC cardiac differentiation. These</div><div>results suggest that the developed dual-sensitive hydrogels may be promising carriers for cardiac cell therapy.</div>