A prevascularization strategy using novel fibrous porous silk scaffolds for tissue regeneration in mice with spinal cord injury.
- 作者列表："Zhong J","Xu J","Lu S","Wang Z","Zheng Y","Tang Q","Zhu J","Zhu T
:Spinal cord injury (SCI) represents an extremely debilitating condition for which no efficacious treatment is available. Due to the unsatisfactory capacity for revascularization following SCI, restoring vascular perfusion seems to be a promising way to modulate the lesion environment to promote a regenerative phenotype. Although engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic factors, slow and insufficient vascularization of large tissue constructs negatively impacts the survival and function of these transplanted cells. In this study, we cocultured our fibrous porous silk scaffold (FPSS) with ADAMTS13-overexpressing human umbilical vein endothelial cells (HUVECs) in vitro and transplanted this prevascularized construct into an SCI mouse model. The prevascularized system exhibited a tube-like structure in vitro, promoted vascular infiltration and microvascular network formation after transplantation, and increased recruitment of neural cells to the lesion site. Twenty-eight days later, behavioural analysis showed that locomotor recovery was significantly improved in treated animals compared with control animals. Taken together, our results suggest that the FPSS-HUVEC system promoted neovascularization, improved the microenvironment, and guided axon growth at the injury site. Therefore, this prevascularization system may provide a better therapeutic option for SCI.
: 脊髓损伤 (SCI) 代表一种极度衰弱的状况，目前尚无有效的治疗方法。由于 SCI 后血运重建能力不理想，恢复血管灌注似乎是调节病变环境以促进再生表型的一种有希望的方式。尽管工程化支架提供了递送治疗细胞和神经营养因子的平台，但大型组织构建体血管化缓慢和不足对这些移植细胞的存活和功能产生了负面影响。在本研究中，我们将我们的纤维多孔蚕丝支架 (FPSS) 与 ADAMTS13-overexpressing 人脐静脉内皮细胞 (HUVECs) 体外共培养，并将这种预血管化的构建体移植到 SCI 小鼠模型中。预培养系统在体外表现出管状结构，促进移植后血管浸润和微血管网络形成，增加神经细胞向病变部位的募集。28 天后，行为分析显示，与对照动物相比，处理动物的运动恢复显著改善。总之，我们的结果表明，FPSS-HUVEC 系统促进了新生血管形成，改善了微环境，并引导了损伤部位的轴突生长。因此，这种预断流系统可能为 SCI 提供更好的治疗选择。
METHODS:Objective To clarify the existence of monophasic neuromyelitis optica spectrum disorders (NMOSD) and to identify predictive factors of long-term relapse-free form. Methods We retrospectively analyzed 289 Chinese patients with NMOSD. Selected subjects were divided into three groups based on the time interval between disease onset and the first relapse, if any. Clinical and imaging data were acquired from each patient’s medical record and evaluated as predictive factors for NMOSD. Results In total, none of the participating patients exhibited a monophasic form of NMOSD. Rather, 241 patients were selected for relapse tendency analysis; 143 (59.3%) patients relapsed within the first year, 66 (27.4%) during 1–5 years, and 32 (13.3%) beyond 5 years. Such onset symptoms as optic neuritis (ON) and non-longitudinally extensive transverse myelitis (LETM) were independent prognostic factors for a prolonged remission interval.
METHODS::Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.
METHODS:Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005−2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.