Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
ACS Appl Mater Interfaces. 2023 Aug 9;15(31):37193-37204. doi: 10.1021/acsami.3c06189. Epub 2023 Jul 26.
Mesenchymal stem cell (MSC)-based therapy has emerged as a promising strategy for the treatment of spinal cord injury (SCI). However, the hostile microenvironment of SCI, which can adversely affect the survival and paracrine effect of the implanted MSCs, severely limits the therapeutic efficacy of this approach. Here, we report on a ceria nanozyme-integrated thermoresponsive forming hydrogel (CeNZ-gel) that can enable dual enhancement of MSC viability and paracrine effect, leading to highly efficient spinal cord repair. The sol-gel transition property of the CeNZ-gel at body temperature ensures uniform coverage of the hydrogel in injured spinal cord tissues. Our results demonstrate that the CeNZ-gel significantly increases the viability of transplanted MSCs in the microenvironment by attenuating oxidative stress and, more importantly, promotes the secretion of angiogenic factors from MSCs by inducing autophagy of MSCs. The synergy between the oxidative stress-relieving effect of CeNZs and the paracrine effect of MSCs accelerates angiogenesis, nerve repair, and motor function recovery after SCI, providing an efficient strategy for MSC-based SCI therapy.
基于间充质干细胞（MSC）的治疗方法已成为治疗脊髓损伤（SCI）的一种有前途的策略。然而，SCI 的恶劣微环境会对植入的 MSC 的存活和旁分泌效应产生不利影响，严重限制了这种方法的治疗效果。在这里，我们报告了一种基于铈纳米酶的温敏形成水凝胶（CeNZ-gel），它可以实现对 MSC 活力和旁分泌效应的双重增强，从而实现高效的脊髓修复。CeNZ-gel 在体温下的溶胶-凝胶转变特性确保了水凝胶在损伤的脊髓组织中的均匀覆盖。我们的结果表明，CeNZ-gel 通过减轻氧化应激显著提高了移植 MSC 在微环境中的活力，更重要的是，通过诱导 MSC 自噬来促进 MSC 分泌血管生成因子。CeNZs 的缓解氧化应激作用和 MSC 的旁分泌效应之间的协同作用加速了 SCI 后的血管生成、神经修复和运动功能恢复，为基于 MSC 的 SCI 治疗提供了一种有效的策略。
