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Current Status and Future Strategies to Treat Spinal Cord Injury with Adult Stem Cells

机译:成人干细胞治疗脊髓损伤的现状和未来策略

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摘要

Spinal cord injury (SCI) is one of the most devastating conditions and many SCI patients suffer neurological sequelae. Stem cell therapies are expected to be beneficial for many patients with central nervous system injuries, including SCI. Adult stem cells (ASCs) are not associated with the risks which embryonic stem cells have such as malignant transformation, or ethical problems, and can be obtained relatively easily. Consequently, many researchers are currently studying the effects of ASCs in clinical trials. The environment of transplanted cells applied in the injured spinal cord differs between the phases of SCI; therefore, many researchers have investigated these phases to determine the optimal time window for stem cell therapy in animals. In addition, the results of clinical trials should be evaluated according to the phase in which stem cells are transplanted. In general, the subacute phase is considered to be optimal for stem cell transplantation. Among various candidates of transplantable ASCs, mesenchymal stem cells (MSCs) are most widely studied due to their clinical safety. MSCs are also less immunogenic than neural stem/progenitor cells and consequently immunosuppressants are rarely required. Attempts have been made to enhance the effects of stem cells using scaffolds, trophic factors, cytokines, and other drugs in animal and/or human clinical studies. Over the past decade, several clinical trials have suggested that transplantation of MSCs into the injured spinal cord elicits therapeutic effects on SCI and is safe; however, the clinical effects are limited at present. Therefore, new therapeutic agents, such as genetically enhanced stem cells which effectively secrete neurotrophic factors or cytokines, must be developed based on the safety of pure MSCs.
机译:脊髓损伤(SCI)是最严重的疾病之一,许多SCI患者都患有神经系统后遗症。预期干细胞疗法将对包括SCI在内的许多中枢神经系统损伤患者有益。成年干细胞(ASC)与胚胎干细胞具有的恶性转化或道德问题等风险无关,可以相对容易地获得。因此,许多研究人员目前正在临床试验中研究ASC的作用。在脊髓损伤的不同阶段,应用于受损脊髓的移植细胞的环境有所不同。因此,许多研究人员已经研究了这些阶段,以确定动物干细胞治疗的最佳时间窗口。此外,应根据干细胞移植的阶段评估临床试验结果。通常,亚急性期被认为是干细胞移植的最佳选择。在各种可移植ASC候选物中,间充质干细胞(MSC)由于其临床安全性而得到了最广泛的研究。 MSCs的免疫原性也比神经干/祖细胞低,因此很少需要免疫抑制剂。在动物和/或人类临床研究中,已经尝试使用支架,营养因子,细胞因子和其他药物来增强干细胞的作用。在过去的十年中,一些临床试验表明,将MSCs移植到受伤的脊髓中可引起SCI的治疗效果,并且是安全的。但是,目前临床效果有限。因此,必须基于纯MSC的安全性开发新的治疗剂,例如有效分泌神经营养因子或细胞因子的基因增强干细胞。

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