Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China; Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Lab of Stem Cell Biology and Innovative Research of Chinese Medicine; National Institute for Stem Cell Clinical Research, Guangdong Provincial Hospital of Chinese Medicine/The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China; Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510080, China.
Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China; Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Biomaterials. 2023 Aug;299:122161. doi: 10.1016/j.biomaterials.2023.122161. Epub 2023 May 19.
We previously constructed a three-dimensional gelatin sponge (3D-GS) scaffold as a delivery vehicle for therapeutic cells and trophic factors in the treatment of spinal cord injury (SCI), and this study aimed to assess the biosafety and efficacy of the scaffold in a non-human primate SCI model. However, because it has only been tested in rodent and canine models, the biosafety and efficacy of the scaffold should ideally be assessed in a non-human primate SCI model before its use in the clinic. No adverse reactions were observed over 8 weeks following 3D-GS scaffold implantation into in a Macaca fascicularis with hemisected SCI. Scaffold implantation also did not add to neuroinflammatory or astroglial responses already present at the injured site, suggesting good biocompatibility. Notably, there was a significant reduction in α-smooth muscle actin (αSMA)-positive cells at the injury/implantation interface, leading to alleviation of fibrotic compression of the residual spinal cord tissue. The regenerating tissue in the scaffold showed numerous cells migrating into the implant secreting abundant extracellular matrix, resulting in a pro-regenerative microenvironment. Consequently, nerve fiber regeneration, myelination, vascularization, neurogenesis, and electrophysiological improvements were achieved. These results indicated that the 3D-GS scaffold had good histocompatibility and effectiveness in the structural repair of injured spinal cord tissue in a non-human primate and is suitable for use in the treatment of patients with SCI.
我们之前构建了一个三维明胶海绵（3D-GS）支架作为治疗细胞和神经营养因子在脊髓损伤（SCI）治疗中的载体，本研究旨在评估该支架在非人类灵长类 SCI 模型中的生物安全性和疗效。然而，由于它仅在啮齿动物和犬模型中进行了测试，因此在将支架用于临床之前，理想情况下应在非人类灵长类 SCI 模型中评估其生物安全性和疗效。在半切 SCI 的猕猴中植入 3D-GS 支架 8 周后未观察到不良反应。支架植入也没有增加损伤部位已经存在的神经炎症或星形胶质细胞反应，表明良好的生物相容性。值得注意的是，损伤/植入界面处的α-平滑肌肌动蛋白（αSMA）阳性细胞显著减少，导致残余脊髓组织的纤维性压迫得到缓解。支架内再生组织中有大量细胞迁移到植入物中，分泌丰富的细胞外基质，形成有利于再生的微环境。因此，实现了神经纤维再生、髓鞘形成、血管化、神经发生和电生理改善。这些结果表明，3D-GS 支架在非人类灵长类动物的损伤脊髓组织的结构修复中具有良好的组织相容性和有效性，适合用于治疗 SCI 患者。
