Mobarakeh Zahra Taherian, Hasanzadeh Elham, Farzin Ali, Goodarzi Arash, Farahani Morteza Sagharjoghi, Shirian Sadegh, Mahmoodi Narges, Zamani Narges, Karimi Anita, Ai Jafar
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Immunogenetics Research Center, Department of Tissue Engineering & Regenerative Medicine, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Injury. 2023 Feb 26. doi: 10.1016/j.injury.2023.01.041.
Based on recent advances in tissue engineering and stem cell therapy in nervous system diseases treatments, this study aimed to investigate sciatic nerve regeneration using human endometrial stem cells (hEnSCs) encapsulated fibrin gel containing chitosan nanoparticle loaded by insulin (Ins-CPs). Stem cells and also Insulin (Ins), which is a strong signaling molecule in peripheral nerve regeneration, play an important role in neural tissue engineering.
The fibrin hydrogel scaffold containing insulin loaded chitosan particles was synthesized and characterized. Release profiles of insulin from hydrogel was determined through UV-visible spectroscopy. Also, human endometrial stem cells encapsulated in hydrogel and its cell biocompatibility were assigned. Furthermore, the sciatic nerve crush injury was carried out and prepared fibrin gel was injected at the crush injury site by an 18-gage needle. Eight and twelve weeks later, the recovery of motor and sensory function and histopathological evaluation were assessed.
The in vitro experiments showed that the insulin can promote hEnSCs proliferation within a certain concentration range. Animals' treatment confirmed that developed fibrin gel containing Ins-CPs and hEnSCs significantly improves motor function and sensory recovery. Hematoxylin and Eosin (H&E) images provided from cross-sectional and, longitudinal-sections of the harvested regenerative nerve showed that regenerative nerve fibers had been formed and accompanied with new blood vessels in the fibrin/insulin/hEnSCs group.
Our results demonstrated that the prepared hydrogel scaffolds containing insulin nanoparticles and hEnSCs could be considered as a potential biomaterial aimed at regeneration of sciatic nerves.
基于组织工程和干细胞疗法在神经系统疾病治疗方面的最新进展,本研究旨在利用包裹在含有胰岛素负载壳聚糖纳米颗粒(Ins-CPs)的纤维蛋白凝胶中的人子宫内膜干细胞(hEnSCs)来研究坐骨神经再生。干细胞以及胰岛素(Ins),后者是周围神经再生中的一种强信号分子,在神经组织工程中发挥着重要作用。
合成并表征了含有胰岛素负载壳聚糖颗粒的纤维蛋白水凝胶支架。通过紫外可见光谱法测定胰岛素从水凝胶中的释放曲线。此外,对包裹在水凝胶中的人子宫内膜干细胞及其细胞生物相容性进行了评估。此外,进行了坐骨神经挤压损伤,并通过18号针头将制备好的纤维蛋白凝胶注射到挤压损伤部位。8周和12周后,评估运动和感觉功能的恢复情况以及组织病理学评估。
体外实验表明,胰岛素在一定浓度范围内可促进hEnSCs增殖。动物实验证实,含有Ins-CPs和hEnSCs的新型纤维蛋白凝胶能显著改善运动功能和感觉恢复。从收获的再生神经的横截面和纵截面提供的苏木精和伊红(H&E)图像显示,在纤维蛋白/胰岛素/hEnSCs组中已形成再生神经纤维并伴有新血管。
我们的结果表明,所制备的含有胰岛素纳米颗粒和hEnSCs的水凝胶支架可被视为一种用于坐骨神经再生的潜在生物材料。