Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord.
Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord.
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DOI：
10.1093/brain/awr339
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Pluchino S
中科院分区：
文献类型：
--
作者：
Cusimano M;Biziato D;Brambilla E;Donegà M;Alfaro-Cervello C;Snider S;Salani G;Pucci F;Comi G;Garcia-Verdugo JM;De Palma M;Martino G;Pluchino S
移植的神经干/前体细胞具有独特的治疗可塑性，除了细胞替代外，还可以同时指导多种治疗机制。在这里，我们询问了神经干细胞/前体细胞的治疗可塑性后，他们在严重挫伤的脊髓局灶性植入。我们在挫伤的小鼠脊髓的近端和远端注射同系神经干细胞/前体细胞，并分析小鼠的运动功能和相关的继发性病理事件，移植的神经干细胞/前体细胞的细胞命运，以及损伤部位的基因表达和炎性细胞浸润。我们使用了两种不同剂量的神经干细胞/前体细胞和两种治疗方案，无论是亚急性（7天）或早期慢性（21天）神经干细胞/前体细胞移植后诱导实验性胸部严重脊髓损伤。只有神经干/前体细胞亚急性移植促进脊髓损伤小鼠运动功能的恢复。移植的神经干细胞/前体细胞在病变周围环境的水平上未分化地存活，并通过细胞连接偶联与内源性吞噬细胞建立联系。这与体内重要炎性细胞转录物表达水平的显著调节有关。移植的神经干细胞/前体细胞通过减少“经典活化”（M1样）巨噬细胞的比例，使损伤部位的炎性细胞浸润偏斜，同时促进损伤脊髓的愈合。在这里，我们确定了一个精确的窗口的机会与治疗可塑性体干细胞治疗复杂的脊髓损伤，并建议神经干细胞/前体细胞有能力重新编程局部炎症细胞微环境从“敌对”到“指导”的作用，从而促进愈合或再生过去的病变。
Transplanted neural stem/precursor cells possess peculiar therapeutic plasticity and can simultaneously instruct several therapeutic mechanisms in addition to cell replacement. Here, we interrogated the therapeutic plasticity of neural stem/precursor cells after their focal implantation in the severely contused spinal cord. We injected syngeneic neural stem/precursor cells at the proximal and distal ends of the contused mouse spinal cord and analysed locomotor functions and relevant secondary pathological events in the mice, cell fate of transplanted neural stem/precursor cells, and gene expression and inflammatory cell infiltration at the injured site. We used two different doses of neural stem/precursor cells and two treatment schedules, either subacute (7 days) or early chronic (21 days) neural stem/precursor cell transplantation after the induction of experimental thoracic severe spinal cord injury. Only the subacute transplant of neural stem/precursor cells enhanced the recovery of locomotor functions of mice with spinal cord injury. Transplanted neural stem/precursor cells survived undifferentiated at the level of the peri-lesion environment and established contacts with endogenous phagocytes via cellular–junctional coupling. This was associated with significant modulation of the expression levels of important inflammatory cell transcripts in vivo. Transplanted neural stem/precursor cells skewed the inflammatory cell infiltrate at the injured site by reducing the proportion of ‘classically-activated’ (M1-like) macrophages, while promoting the healing of the injured cord. We here identify a precise window of opportunity for the treatment of complex spinal cord injuries with therapeutically plastic somatic stem cells, and suggest that neural stem/precursor cells have the ability to re-programme the local inflammatory cell microenvironment from a ‘hostile’ to an ‘instructive’ role, thus facilitating the healing or regeneration past the lesion.
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影响因子：
4.2
作者：
Nishi, Rebecca A.;Liu, Hongli;Anderson, Aileen J.
通讯作者：
Anderson, Aileen J.
影响因子：
0.7
作者：
Nucera, Silvia;Biziato, Daniela;De Palma, Michele
通讯作者：
De Palma, Michele
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
DOI：
10.1073/pnas.0915134107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Jaderstad, Johan;Jaderstad, Linda M.;Herlenius, Eric
通讯作者：
Herlenius, Eric
影响因子：
3.7
作者：
Aharonowiz M;Einstein O;Fainstein N;Lassmann H;Reubinoff B;Ben-Hur T
通讯作者：
Ben-Hur T