Human embryonic stem cell-derived oligodendrocyte progenitors aid in functional recovery of sensory pathways following contusive spinal cord injury.
Human embryonic stem cell-derived oligodendrocyte progenitors aid in functional recovery of sensory pathways following contusive spinal cord injury.
复制标题
DOI：
10.1371/journal.pone.0047645
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kerr C
中科院分区：
文献类型：
--
作者：
All AH;Bazley FA;Gupta S;Pashai N;Hu C;Pourmorteza A;Kerr C
人类干细胞衍生物移植在啮齿类动物模型中被广泛研究，以恢复脊髓损伤（SCI）后神经通路的功能。研究已经证实了脊髓损伤移植后细胞存活。我们试图评估移植的人胚胎干细胞（hES）来源的少突胶质细胞祖细胞（OPCs）在大鼠挫伤中的存活和潜在的治疗效果。利用生物发光成像技术验证细胞存活至4周，并在皮层记录体感诱发电位（ssep）以监测整个6周恢复期的感觉通路功能。用萤火虫荧光素酶基因诱导hES细胞分化为OPCs。在诱导中度挫伤性脊髓损伤2小时后，将OPCs移植到大鼠脊髓损伤中心。与对照组相比，hes治疗组表现出改善的ssep，包括振幅增加和潜伏期减少。移植的OPCs在损伤脊髓中的生物发光减少了97%，而注射到未损伤脊髓中的生物发光仅减少了80%。两个实验组的生物发光均有所增加，到第3周时，差异无统计学意义，表明细胞存活和增殖独立于损伤。脊髓的死后组织学显示，表达成熟少突胶质细胞标记物和髓鞘碱性蛋白的人细胞整合，没有表达星形胶质细胞（GFAP）或多能细胞（OCT4）标记物。在挫伤性脊髓损伤2小时后移植的hes来源的OPCs存活并分化为产生MBP的ol。早在损伤后1周，与对照组相比，治疗大鼠在SSEP振幅和潜伏期方面表现出功能改善。最后，损伤后2小时的敌对损伤微环境最初导致细胞死亡增加，但不影响细胞的长期增殖或存活，这表明细胞可以比常规接受的更快地移植。
Transplantations of human stem cell derivatives have been widely investigated in rodent models for the potential restoration of function of neural pathways after spinal cord injury (SCI). Studies have already demonstrated cells survival following transplantation in SCI. We sought to evaluate survival and potential therapeutic effects of transplanted human embryonic stem (hES) cell-derived oligodendrocyte progenitor cells (OPCs) in a contusive injury in rats. Bioluminescence imaging was utilized to verify survivability of cells up to 4 weeks, and somatosensory evoked potential (SSEPs) were recorded at the cortex to monitor function of sensory pathways throughout the 6-week recovery period. hES cells were transduced with the firefly luciferase gene and differentiated into OPCs. OPCs were transplanted into the lesion epicenter of rat spinal cords 2 hours after inducing a moderate contusive SCI. The hES-treatment group showed improved SSEPs, including increased amplitude and decreased latencies, compared to the control group. The bioluminescence of transplanted OPCs decreased by 97% in the injured spinal cord compared to only 80% when injected into an uninjured spinal cord. Bioluminescence increased in both experimental groups such that by week 3, no statistical difference was detected, signifying that the cells survived and proliferated independent of injury. Post-mortem histology of the spinal cords showed integration of human cells expressing mature oligodendrocyte markers and myelin basic protein without the expression of markers for astrocytes (GFAP) or pluripotent cells (OCT4). hES-derived OPCs transplanted 2 hours after contusive SCI survive and differentiate into OLs that produce MBP. Treated rats demonstrated functional improvements in SSEP amplitudes and latencies compared to controls as early as 1 week post-injury. Finally, the hostile injury microenvironment at 2 hours post-injury initially caused increased cell death but did not affect the long-term cell proliferation or survival, indicating that cells can be transplanted sooner than conventionally accepted.
登录
查看更多内容
DOI：
10.1016/s0003-9993(98)90213-1
发表时间：
1998-01-01
影响因子：
4.3
作者：
Curt, A;Keck, ME;Dietz, V
通讯作者：
Dietz, V
影响因子：
4.4
作者：
All, Angelo H.;Walczak, Piotr;Agrawal, Gracee;Gorelik, Michael;Lee, Christopher;Thakor, Nitish V.;Bulte, Jeff W. M.;Kerr, Douglas A.
通讯作者：
Kerr, Douglas A.
影响因子：
3.7
作者：
Kumagai G;Okada Y;Yamane J;Nagoshi N;Kitamura K;Mukaino M;Tsuji O;Fujiyoshi K;Katoh H;Okada S;Shibata S;Matsuzaki Y;Toh S;Toyama Y;Nakamura M;Okano H
通讯作者：
Okano H
DOI：
10.1073/pnas.76.1.514
发表时间：
1979-01-01
影响因子：
11.1
作者：
BOTTENSTEIN, JE;SATO, GH
通讯作者：
SATO, GH
DOI：
10.1016/s0924-980x(98)00002-2
发表时间：
1998-04-01
期刊：
ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
Dietz, V;Wirz, M;Curt, A
通讯作者：
Curt, A