pH-Sensitive and Thermosensitive Hydrogels as Stem-Cell Carriers for Cardiac Therapy.
pH-Sensitive and Thermosensitive Hydrogels as Stem-Cell Carriers for Cardiac Therapy.
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pH 敏感和热敏感水凝胶作为心脏治疗的干细胞载体
DOI：
10.1021/acsami.6b01374
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发表时间：
2016-05-04
影响因子：
9.5
通讯作者：
Guan J
中科院分区：
文献类型：
--
作者：
Li Z;Fan Z;Xu Y;Lo W;Wang X;Niu H;Li X;Xie X;Khan M;Guan J
干细胞疗法有可能使心脏病发作后受损的心脏组织再生。可注射水凝胶可用作干细胞载体，以改善细胞在心脏组织中的保留。然而，目前的水凝胶作为细胞载体并不理想，因为它们中的大多数在固化后会阻塞血管。此外，这些水凝胶具有相对较慢的凝胶化速率（通常>60秒），这不允许它们在注射时快速固化，从而有效地将细胞保持在心脏组织中。结果，水凝胶和细胞被挤出组织，导致低细胞保留。为了解决这些问题，我们开发了水凝胶，它可以在37 °C时在梗死心脏的pH值（6−7）下快速固化，但不能在37 °C时在血液的pH值（7.4）下固化。这些水凝胶在临床上也很有吸引力，因为它们可以通过通常用于微创手术的导管注射。以N-异丙基丙烯酰胺、丙基丙烯酸、甲基丙烯酸羟乙酯-三亚甲基碳酸酯和甲基丙烯酸聚环氧乙烷甲氧基酯为单体，通过自由基聚合制备了水凝胶。水凝胶溶液可在37 °C下在pH 8.0下通过0.2 mm直径的导管注射，并且它们可在37 °C下在pH 6.5下快速形成固体凝胶。所有的水凝胶表现出pH依赖性的降解和机械性能，在pH 6.5比在pH 7.4更少的质量损失和更大的复杂的剪切模量。当将心球衍生的细胞（CDC）包封在水凝胶中时，细胞能够在7天的培养期内存活。存活细胞分化为心肌细胞，心肌标志物在基因和蛋白水平上的表达证明了这一点，如心肌肌钙蛋白T、肌球蛋白重链α、钙通道CACNA 1c、心肌肌钙蛋白I和连接蛋白43。发现凝胶完整性在很大程度上影响CDC心脏分化。这些结果表明，开发的双敏感水凝胶可能是有前途的载体心脏细胞治疗。
Stem-cell therapy has the potential to regenerate damaged heart tissue after a heart attack. Injectable hydrogels may be used as stem-cell carriers to improve cell retention in the heart tissue. However, current hydrogels are not ideal to serve as cell carriers because most of them block blood vessels after solidification. In addition, these hydrogels have a relatively slow gelation rate (typically >60 s), which does not allow them to quickly solidify upon injection, so as to efficiently hold cells in the heart tissue. As a result, the hydrogels and cells are squeezed out of the tissue, leading to low cell retention. To address these issues, we have developed hydrogels that can quickly solidify at the pH of an infarcted heart (6−7) at 37 °C but cannot solidify at the pH of blood (7.4) at 37 °C. These hydrogels are also clinically attractive because they can be injected through catheters commonly used for minimally invasive surgeries. The hydrogels were synthesized by free-radical polymerization of N-isopropylacrylamide, propylacrylic acid, hydroxyethyl methacrylate-cooligo(trimethylene carbonate), and methacrylate poly(ethylene oxide) methoxy ester. Hydrogel solutions were injectable 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 hydrogels showed pH-dependent degradation and mechanical properties with less mass loss and greater complex shear modulus at pH 6.5 than at pH 7.4. When cardiosphere-derived cells (CDCs) were encapsulated in the hydrogels, the cells were able to survive during a 7-day culture period. The surviving cells were differentiated into cardiac cells, as evidenced by the expression of cardiac markers at both the gene and protein levels, such as cardiac troponin T, myosin heavy chain α, calcium channel CACNA1c, cardiac troponin I, and connexin 43. The gel integrity was found to largely affect CDC cardiac differentiation. These results suggest that the developed dual-sensitive hydrogels may be promising carriers for cardiac cell therapy.
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影响因子：
3.7
作者：
Davis DR;Zhang Y;Smith RR;Cheng K;Terrovitis J;Malliaras K;Li TS;White A;Makkar R;Marbán E
通讯作者：
Marbán E
影响因子：
10.8
作者：
Murthy, N;Robichaud, JR;Hoffman, AS
通讯作者：
Hoffman, AS
影响因子：
3.3
作者：
Martens TP;Godier AF;Parks JJ;Wan LQ;Koeckert MS;Eng GM;Hudson BI;Sherman W;Vunjak-Novakovic G
通讯作者：
Vunjak-Novakovic G
影响因子：
15.9
作者：
Kehat, I;Kenyagin-Karsenti, D;Gepstein, L
通讯作者：
Gepstein, L
影响因子：
4
作者：
Huang, Wei;Wang, Tao;Wang, Yigang
通讯作者：
Wang, Yigang