Transplantation of mature adipocyte-derived dedifferenceated fat cells promote locomotor functional recovery by remyelination and glial scar reduction after spinal cord injuty in mice
Transplantation of mature adipocyte-derived dedifferenceated fat cells promote locomotor functional recovery by remyelination and glial scar reduction after spinal cord injuty in mice
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移植成熟脂肪细胞来源的去分化脂肪细胞通过髓鞘再生和减少脊髓损伤后神经胶质疤痕促进运动功能恢复
DOI：
10.1016/j.bbrc.2014.10.082
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
KanoK
中科院分区：
文献类型：
--
作者：
Yamada H;Ito D;Oki Y;Kitagawa M;Matsumoto T;Watari T;KanoK
成熟脂肪细胞来源的去分化脂肪细胞（DFAT）有可能作为脊髓损伤（SCI）细胞治疗的新细胞来源，但其机制尚不清楚。本研究的目的是检查DFAT诱导的功能恢复是否通过脊髓损伤小鼠模型中的髓鞘再生和/或胶质瘢痕减少来实现。为了实现这一点，我们使成年雌性小鼠（n= 22）经受SCI。伤后第8天进行运动试验，将小鼠随机分为对照组和DFAT组。DFAT组给予DFAT立体定位注射，对照组给予DMEM培养液。以重复的间隔进行功能测试，直到第36天，并对脊髓切片进行免疫组织化学或染色。与对照组相比，DFAT移植显著改善了其后肢的运动功能，促进了髓鞘再生和胶质瘢痕减少。促进髓鞘再生或/和减少胶质瘢痕与运动功能的恢复之间存在显著的正相关。此外，移植DFAT表达神经元，星形胶质细胞和少突胶质细胞的标记，沿着神经营养因子，在损伤的脊髓。总之，DFAT诱导的功能恢复，在SCI后的小鼠可能是介导的细胞自主和细胞非自主的影响，对损伤的脊髓髓鞘再生。
Mature adipocyte-derived dedifferentiated fat cells (DFAT) have a potential to be useful as new cell-source for cell-based therapy for spinal cord injury (SCI), but the mechanisms remain unclear. The objective of this study was to examine whether DFAT-induced functional recovery is achieved through remyelination and/or glial scar reduction in a mice model of SCI. To accomplish this we subjected adult female mice (n= 22) to SCI. On the 8th day post-injury locomotor tests were performed, and the mice were randomly divided into two groups (control and DFAT). The DFAT group received stereotaxic injection of DFAT, while the controls received DMEM medium. Functional tests were conducted at repeated intervals, until the 36th day, and immunohistochemistry or staining was performed on the spinal cord sections. DFAT transplantation significantly improved locomotor function of their hindlimbs, and promoted remyelination and glial scar reduction, when compared to the controls. There were significant and positive correlations between promotion of remyelination or/and reduction of glial scar, and recovery of locomotor function. Furthermore, transplanted DFAT expressed markers for neuron, astrocyte, and oligodendrocyte, along with neurotrophic factors, within the injured spinal cord. In conclusion, DFAT-induced functional recovery in mice after SCI is probably mediated by both cell-autonomous and cell-non-autonomous effects on remyelination of the injured spinal cord.