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自身反应性T细胞在体外诱导骨髓间充质干细胞转分化为神经干细胞。

Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells.

作者信息

Moviglia G A, Varela G, Gaeta C A, Brizuela J A, Bastos F, Saslavsky J

机构信息

Instituto Regina Mater, Paraguay 2452, Buenos Aires, 1121 ABL, Argentina.

出版信息

Cytotherapy. 2006;8(3):196-201. doi: 10.1080/14653240600735958.

DOI:10.1080/14653240600735958
PMID:16793728
Abstract

BACKGROUND

The degree of post-injury inflammation of the damaged area of a spinal cord is the main difference between the natural successful repair in inferior vertebrates and failure in superior vertebrates. The treatment of rats with anti-myelin lymphocytes after experimental spinal cord injury induces their functional recovery. On the other hand, mesenchymal stem cells (MSC) from adult BM implanted in injured areas recover the morphology and function of spinal cord in mammals. The purpose of this study was to determine whether there is a direct relationship between anti-nervous tissue T cells and MSC reparatory properties.

METHODS

Circulating autoreactive lymphocytes of patients with spinal cord injuries and amyotrophic lateral sclerosis were isolated and activated in vitro. These cells were cocultured with autologous MSC for 2-15 days. Cocultures of non-selected lymphocytes were used as controls.

RESULTS

After 48 h of coculture, MSC adopted a spindle shape with polarization of the cytoplasm that resembled bipolar neurons. Their nuclei diminished the nucleolus number and the chromatin lost its granular appearance. After 15 days of culture the cells developed the typical structure of a neural network. No morphologic changes were observed in control cultures. The differentiated cells reacted positively to tubuline III, GFAP and nestin. No differences were observed between the different patient cell sources.

DISCUSSION

We observed that autoreactive cells may induce the transdifferentiation of MSC to neural stem cells. This T-cell-MSC interaction may be a common phenomenon during physiologic nerve tissue repair.

摘要

背景

脊髓损伤区域损伤后炎症程度是低等脊椎动物自然成功修复与高等脊椎动物修复失败的主要区别。实验性脊髓损伤后用抗髓磷脂淋巴细胞治疗大鼠可诱导其功能恢复。另一方面,将成年骨髓间充质干细胞(MSC)植入损伤区域可恢复哺乳动物脊髓的形态和功能。本研究的目的是确定抗神经组织T细胞与MSC修复特性之间是否存在直接关系。

方法

分离并体外激活脊髓损伤患者和肌萎缩侧索硬化患者的循环自身反应性淋巴细胞。将这些细胞与自体MSC共培养2至15天。未选择淋巴细胞的共培养物用作对照。

结果

共培养48小时后,MSC呈纺锤形,细胞质极化,类似于双极神经元。其细胞核减少了核仁数量,染色质失去了颗粒状外观。培养15天后,细胞形成了典型的神经网络结构。对照培养物中未观察到形态学变化。分化后的细胞对微管蛋白III、胶质纤维酸性蛋白和巢蛋白呈阳性反应。不同患者细胞来源之间未观察到差异。

讨论

我们观察到自身反应性细胞可能诱导MSC向神经干细胞转分化。这种T细胞与MSC的相互作用可能是生理神经组织修复过程中的常见现象。

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Cytotherapy. 2006;8(3):196-201. doi: 10.1080/14653240600735958.
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