Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
Sci China Life Sci. 2020 Dec;63(12):1879-1886. doi: 10.1007/s11427-019-1623-5. Epub 2020 May 6.
Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues (aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of aSCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein 2-, 5-hydroxytryptamine-, choline acetyltransferase- and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in aSCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.
脊髓损伤（SCI），尤其是完全横断性 SCI，会导致细胞和细胞外基质的丧失以及功能障碍。在之前的研究中，我们将成体脊髓组织（aSCTs）移植到大鼠 SCI 模型中，以替代丢失的组织并促进恢复。然而，啮齿动物在脊髓系统的规模、解剖结构和功能以及损伤后的反应方面与人类患者存在很大差异。因此，需要使用大动物 SCI 模型来检查潜在治疗方法的修复效率。在这项研究中，我们将成年犬的同种异体 aSCT 移植到犬的胸段脊髓完全横断后的损伤区域，并研究了长期的细胞存活和功能恢复。为了提高修复效率，在 aSCT 移植过程中添加了生长因子鸡尾酒，提供了有利的微环境。结果表明，aSCT 的移植，特别是添加生长因子，显著改善了运动功能的恢复，并增加了术后 6 个月损伤区域中神经丝、微管相关蛋白 2、5-羟色胺、胆碱乙酰转移酶和酪氨酸羟化酶阳性神经元的数量。此外，我们证明了 aSCT 中的供体细胞在移植后可以存活很长时间。这项研究首次表明，移植 aSCT 结合生长因子补充有助于受损脊髓的重建，从而促进大动物完全横断性 SCI 模型中持久的运动功能恢复，因此可以被认为是人类的一种潜在治疗策略。
