School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China; Institute of Neuroscience, Zhengzhou University, Zhengzhou, 450052, Henan, China.
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
Acta Biomater. 2021 Sep 1;131:185-197. doi: 10.1016/j.actbio.2021.06.038. Epub 2021 Jul 1.
Stem cell therapy is promising for neural repair in devastating traumatic brain injury (TBI). However, the low survival and differentiation rates of transplanted stem cells are main obstacles to efficient stem cell therapy in TBI. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are key factors that regulate the survival, recruitment, and differentiation of stem cells. Herein, we synthesized a sodium alginate (SA)/collagen type I (Col)/SDF-1 hydrogel and investigated whether the SA/Col/SDF-1 hydrogel loaded with bone marrow-derived mesenchymal stem cells (BMSCs) had therapeutic effects on a TBI model. Our results showed that the SA/Col/SDF-1 scaffold could stably release SDF-1 and provide biocompatible and biodegradable microenvironment for the survival, migration, and neuronal differentiation of BMSCs in vitro. In a rat model of TBI, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated motor and cognition dysfunction and relieved anxiety and depressive-like behaviors. In addition, the BMSCs/SA/Col/SDF-1 scaffold reduced brain lesions and neuronal cell death and mitigated neuroinflammation. Further studies demonstrated that the BMSCs/SA/Col/SDF-1 hydrogel promoted the migration of BMSCs in the lesions and partly enhanced neurogenesis by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Taken together, our results indicate that the SA/Col/SDF-1 scaffold loaded with BMSCs exerts neuroreparative effects in a TBI rat model, and thus, it may serve as an alternative neural regeneration scaffold for brain injury repair. STATEMENT OF SIGNIFICANCE: Hydrogel facilitates the biological behaviors of transplanted stem cells for tissue regeneration. In this study, we synthesized sodium alginate (SA)/collagen type I (Col)/ scaffold to simultaneously deliver stromal cell derived factor-1 (SDF-1) and bone marrow mesenchymal stem cells (BMSCs) in a rat model of traumatic brain injury (TBI). We found that the SA/Col/SDF-1 hydrogel could continuously release SDF-1 and was conducive to the survival, migration and neuronal differentiation of BMSCs in vitro. In addition, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated neurological deficits, mitigated neuroinflammation, promoted the recruitment of BMSCs and enhanced neurogenesis in TBI partly by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Our results may serve as an alternative neural regeneration strategy for brain injury.
干细胞疗法有望用于治疗毁灭性的创伤性脑损伤（TBI）中的神经修复。然而，移植干细胞的低存活率和分化率是 TBI 中有效干细胞疗法的主要障碍。基质细胞衍生因子-1（SDF-1）及其受体 CXCR4 是调节干细胞存活、募集和分化的关键因素。在此，我们合成了一种海藻酸钠（SA）/胶原 I（Col）/SDF-1 水凝胶，并研究了负载骨髓间充质干细胞（BMSCs）的 SA/Col/SDF-1 水凝胶是否对 TBI 模型具有治疗作用。我们的结果表明，SA/Col/SDF-1 支架可以稳定释放 SDF-1，并为 BMSCs 的存活、迁移和神经元分化提供生物相容性和可生物降解的微环境。在 TBI 大鼠模型中，负载 BMSCs 的 SA/Col/SDF-1 水凝胶显著改善了运动和认知功能障碍，并缓解了焦虑和抑郁样行为。此外，SA/Col/SDF-1 水凝胶支架减轻了脑损伤和神经元细胞死亡，并减轻了神经炎症。进一步的研究表明，BMSCs/SA/Col/SDF-1 水凝胶通过激活 SDF-1/CXCR4 介导的 FAK/PI3K/AKT 通路促进了 BMSCs 在病变中的迁移，并部分增强了神经发生。总之，我们的结果表明，负载 BMSCs 的 SA/Col/SDF-1 支架在 TBI 大鼠模型中发挥神经修复作用，因此，它可能成为脑损伤修复的替代神经再生支架。
水凝胶促进了移植干细胞的生物学行为，以实现组织再生。在这项研究中，我们合成了海藻酸钠（SA）/胶原 I（Col）支架，以在创伤性脑损伤（TBI）大鼠模型中同时递送基质细胞衍生因子-1（SDF-1）和骨髓间充质干细胞（BMSCs）。我们发现，SA/Col/SDF-1 水凝胶可以持续释放 SDF-1，有利于 BMSCs 的体外存活、迁移和神经元分化。此外，负载 BMSCs 的 SA/Col/SDF-1 水凝胶显著改善了神经功能缺损，减轻了神经炎症，促进了 BMSCs 的募集，并通过激活 SDF-1/CXCR4 介导的 FAK/PI3K/AKT 通路部分增强了神经发生，在 TBI 中。我们的研究结果可能为脑损伤提供一种替代的神经再生策略。
