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人牙髓细胞:压迫性脊髓损伤小鼠模型中细胞治疗的新来源。

Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury.

机构信息

Programa de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.

出版信息

J Neurotrauma. 2011 Sep;28(9):1939-49. doi: 10.1089/neu.2010.1317. Epub 2011 Aug 8.

Abstract

Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists and neuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in terms of functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of the extraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal and mesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 and compression of the spinal cord with a vascular clip for 1 min. The cells were transplanted 7 days or 28 days after the lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. We performed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, and ultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better white-matter preservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissue organization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, in addition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. We also demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functional analysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.

摘要

旨在改善创伤后脊髓再生的策略仍然是全世界神经科医生和神经科学家面临的挑战。许多基于细胞的疗法已经过测试,但在功能结果方面取得的成功有限。在这项研究中,我们在压迫性脊髓损伤(SCI)的小鼠模型中研究了人牙髓细胞(HDPCs)的作用。这些细胞具有一些优势,例如提取过程简单,并且表达来自外胚层间充质和间充质成分的营养因子和胚胎标志物。年轻成年雌性 C57/BL6 小鼠在 T9 进行椎板切除术,并使用血管夹对脊髓进行 1 分钟的压迫。细胞在损伤后 7 天或 28 天进行移植,以便比较在亚急性或慢性阶段进行治疗时的恢复情况。我们进行了白质保存、营养因子表达和定量、超微结构和功能分析的定量分析。我们对 HDPC 移植动物的结果表明,与 DMEM 组相比,白质保存更好,组织中营养因子表达水平更高,组织更规整,许多轴突被施万细胞或少突胶质细胞髓鞘化,此外还有一些看起来健康的完整神经元,其胞体上有突触接触。我们还证明 HDPCs 能够表达一些神经胶质标志物,如 GFAP 和 S-100。功能分析还表明这些动物的运动功能得到改善。基于这些发现,我们提出 HDPCs 可能是 SCI 和人类中枢神经系统疾病后治疗干预的可行候选者。

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