Epidermal neural crest stem cell (EPI-NCSC)--mediated recovery of sensory function in a mouse model of spinal cord injury.

Epidermal neural crest stem cell (EPI-NCSC)--mediated recovery of sensory function in a mouse model of spinal cord injury.
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DOI:
10.1007/s12015-010-9152-3
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发表时间:
2010-06
影响因子:
4.8
通讯作者:
Sieber-Blum, Maya
Sieber-Blum, Maya
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Yao Fei;Gourab, Krishnaj;Wells, Clive;Clewes, Oliver;Schmit, Brian D.;Sieber-Blum, Maya

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本研究表明,在挫伤脊髓中移植表皮神经嵴干细胞(EPI-NCSC)可使感觉连通性提高24%,并显著恢复触觉知觉。此外,我们提出了一种利用神经嵴干细胞的迁移能力,基于一种新的培养基和微载体,将EPI-NCSC体外扩增成数百万个干细胞的新方法。脊髓体感诱发电位(SpSEP)和Semmes-Weinstein触摸测试两种独立的方法显示功能改善。移植细胞亚群分化为髓鞘少突胶质细胞。单侧注射EPI-NCSC于小鼠脊髓中线损伤处,可引起双侧改善。脊髓内EPI-NCSC未在脊髓内横向迁移或侵犯脊髓根和背根神经节,这暗示了扩散因素。EPI-NCSC表达神经营养因子、血管生成因子和金属蛋白酶。因此,EPI-NCSC的优势在于它们可以在挫伤脊髓中发挥多种相关功能,包括细胞替代、神经保护、血管生成和疤痕形成调节。EPI-NCSC在脊髓损伤的细胞治疗中具有独特的资格,因为神经嵴细胞和神经管干细胞共享一个更高阶的干细胞,因此在本体论上密切相关。
Here we show that epidermal neural crest stem cell (EPI-NCSC) transplants in the contused spinal cord caused a 24% improvement in sensory connectivity and a substantial recovery of touch perception. Furthermore we present a novel method for the ex vivo expansion of EPI-NCSC into millions of stem cells that takes advantage of the migratory ability of neural crest stem cells and is based on a new culture medium and the use of microcarriers. Functional improvement was shown by two independent methods, spinal somatosensory evoked potentials (SpSEP) and the Semmes-Weinstein touch test. Subsets of transplanted cells differentiated into myelinating oligodendrocytes. Unilateral injections of EPI-NCSC into the lesion of midline contused mouse spinal cords elicited bilateral improvements. Intraspinal EPI-NCSC did not migrate laterally in the spinal cord or invade the spinal roots and dorsal root ganglia, thus implicating diffusible factors. EPI-NCSC expressed neurotrophic factors, angiogenic factors, and metalloproteases. The strength of EPI-NCSC thus is that they can exert a combination of pertinent functions in the contused spinal cord, including cell replacement, neuroprotection, angiogenesis and modulation of scar formation. EPI-NCSC are uniquely qualified for cell-based therapy in spinal cord injury, as neural crest cells and neural tube stem cells share a higher order stem cell and are thus ontologically closely related.
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