大鼠骨髓间充质干细胞可下调大鼠脊髓损伤后caspase-3介导的凋亡途径。
Mesenchymal stem cells from rat bone marrow downregulate caspase-3-mediated apoptotic pathway after spinal cord injury in rats.
作者信息
Dasari Venkata Ramesh, Spomar Daniel G, Cady Craig, Gujrati Meena, Rao Jasti S, Dinh Dzung H
机构信息
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61656, USA.
出版信息
Neurochem Res. 2007 Dec;32(12):2080-93. doi: 10.1007/s11064-007-9368-z. Epub 2007 Jun 13.
Abstract
Mesenchymal stem cells have been intensively studied for their potential use in reparative strategies for neurodegenerative diseases and traumatic injuries. We used mesenchymal stem cells (rMSC) from rat bone marrow to evaluate the therapeutic potential after spinal cord injury (SCI). Immunohistochemistry confirmed a large number of apoptotic neurons and oligodendrocytes in caudal segments 2 mm away from the lesion site. Expression of caspase-3 on both neurons and oligodendrocytes after SCI was significantly downregulated by rMSC. Caspase-3 downregulation by rMSC involves increased expression of FLIP and XIAP in the cytosol and inhibition of PARP cleavage in the nucleus. Animals treated with rMSC had higher Basso, Beattie, Bresnahan (BBB) locomotor scoring and better recovery of hind limb sensitivity. Treatment with rMSC had a positive effect on behavioral outcome and histopathological assessment after SCI. The ability of rMSC to incorporate into the spinal cord, differentiate and to improve locomotor recovery hold promise for a potential cure after SCI.
摘要
间充质干细胞因其在神经退行性疾病和创伤性损伤修复策略中的潜在应用而受到广泛研究。我们使用大鼠骨髓间充质干细胞（rMSC）来评估脊髓损伤（SCI）后的治疗潜力。免疫组织化学证实，在距损伤部位2mm的尾段存在大量凋亡的神经元和少突胶质细胞。rMSC可显著下调SCI后神经元和少突胶质细胞上caspase-3的表达。rMSC对caspase-3的下调涉及细胞质中FLIP和XIAP表达的增加以及细胞核中PARP裂解的抑制。接受rMSC治疗的动物具有更高的Basso、Beattie、Bresnahan（BBB）运动评分，后肢敏感性恢复更好。rMSC治疗对SCI后的行为结果和组织病理学评估具有积极作用。rMSC整合到脊髓中、分化并改善运动恢复的能力为SCI后的潜在治愈带来了希望。
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