Guo Shaowei, Redenski Idan, Landau Shira, Szklanny Ariel, Merdler Uri, Levenberg Shulamit
Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
The First Affiliated Hospital, Shantou University Medical College, Shantou, 515000, China.
Adv Healthc Mater. 2020 Oct;9(20):e2000974. doi: 10.1002/adhm.202000974. Epub 2020 Sep 9.
The regeneration of injured spinal cord is hampered by the lack of vascular supply and neurotrophic support. Transplanting tissue-engineered constructs with developed vascular networks and neurotrophic factors, and further understanding the pattern of vessel growth in the remodeled spinal cord tissue are greatly desired. To this end, highly vascularized scaffolds embedded with human dental pulp stem cells (DPSCs) are fabricated, which possess paracrine-mediated angiogenic and neuroregenerative potentials. The potent pro-angiogenic effect of the prevascularized scaffolds is first demonstrated in a rat femoral bundle model, showing robust vessel growth and blood perfusion induced within these scaffolds postimplantation, as evidenced by laser speckle contrast imaging and 3D microCT dual imaging modalities. More importantly, in a rat complete spinal cord transection model, the implantation of these scaffolds to the injured spinal cords can also promote revascularization, as well as axon regeneration, myelin deposition, and sensory recovery. Furthermore, 3D microCT imaging and novel morphometric analysis on the remodeled spinal cord tissue demonstrate substantial regenerated vessels, more significantly in the sensory tract regions, which correlates with behavioral recovery following prevascularization treatment. Taken together, prevascularized DPSC-embedded constructs bear angiogenic and neurotrophic potentials, capable of augmenting and modulating SCI repair.
受伤脊髓的再生受到血管供应和神经营养支持缺乏的阻碍。人们迫切希望移植具有发达血管网络和神经营养因子的组织工程构建体，并进一步了解重塑脊髓组织中血管生长的模式。为此，制备了嵌入人牙髓干细胞（DPSC）的高度血管化支架，其具有旁分泌介导的血管生成和神经再生潜力。预血管化支架强大的促血管生成作用首先在大鼠股束模型中得到证实，激光散斑对比成像和3D微型计算机断层扫描（microCT）双成像模式显示，植入后这些支架内诱导了强大的血管生长和血液灌注。更重要的是，在大鼠完全脊髓横断模型中，将这些支架植入受伤脊髓也可促进血管再生以及轴突再生、髓鞘沉积和感觉恢复。此外，对重塑脊髓组织的3D microCT成像和新型形态计量分析显示有大量再生血管，在感觉束区域更为明显，这与预血管化治疗后的行为恢复相关。综上所述，预血管化的嵌入DPSC的构建体具有血管生成和神经营养潜力，能够增强和调节脊髓损伤修复。
