Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury.
Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury.
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DOI：
10.1002/stem.245
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发表时间：
2010-01
期刊：
影响因子：
5.2
通讯作者：
Keirstead, Hans S.
中科院分区：
文献类型：
--
作者：
Sharp, Jason;Frame, Jennifer;Siegenthaler, Monica;Nistor, Gabriel;Keirstead, Hans S.
有证据表明，细胞移植可以改善脊髓损伤(SCI)模型的恢复结果，这证实了涉及细胞替代治疗脊髓损伤的治疗策略。大多数脊髓损伤细胞替代的临床前研究都检验了胸部损伤模型。然而，由于大多数人类损伤发生在颈椎水平，评估颈椎损伤模型的潜在治疗方法并使用组织学和功能水平的测量来检验其有效性是至关重要的。为了直接解决颈椎脊髓损伤，我们使用了C5中线挫伤模型，并在该颈椎模型中评估了胸段脊髓损伤的候选治疗方法的疗效。挫伤导致可复制的双侧运动和组织学缺陷，尽管一些损伤参数，如急性损伤严重程度、受影响的灰白质比、内源性再髓鞘形成程度和水平运动缺陷与胸部脊髓损伤的这些参数不对应。根据已报道的胸部脊髓损伤的益处，我们将人类胚胎干细胞(HESC)来源的少突胶质前体细胞(OPC)移植到这个颈椎模型中。HESC来源的OPC移植减轻了病变的发病机制，促进了前肢功能的恢复。移植的组织学效果包括在损伤中心保留健壮的白质和灰质，特别是保存与运动恢复相关的运动神经元。这些发现进一步加深了我们对颈椎脊髓损伤的组织病理学和功能结果的理解，确定了潜在的治疗靶点，并支持使用这些细胞作为颈椎脊髓损伤的治疗方法。
Evidence that cell transplants can improve recovery outcomes in spinal cord injury (SCI) models substantiates treatment strategies involving cell replacement for humans with SCI. Most pre-clinical studies of cell replacement in SCI examine thoracic injury models. However, as most human injuries occur at the cervical level, it is critical to assess potential treatments in cervical injury models and examine their effectiveness using at-level histological and functional measures. To directly address cervical SCI, we used a C5 midline contusion injury model and assessed the efficacy of a candidate therapeutic for thoracic SCI in this cervical model. The contusion generates reproducible, bilateral movement and histological deficits, although a number of injury parameters such as acute severity of injury, affected gray to white matter ratio, extent of endogenous remyelination, and at-level locomotion deficits do not correspond with these parameters in thoracic SCI. Based on reported benefits in thoracic SCI, we transplanted human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into this cervical model. hESC-derived OPC transplants attenuated lesion pathogenesis and improved recovery of forelimb function. Histological effects of transplantation included robust white and gray matter sparing at the injury epicenter, and in particular, preservation of motor neurons that correlated with movement recovery. These findings further our understanding of the histopathology and functional outcomes of cervical SCI, define potential therapeutic targets, and support the use of these cells as a treatment for cervical SCI.
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影响因子：
82.9
作者：
Crowe, MJ;Bresnahan, JC;Beattie, MS
通讯作者：
Beattie, MS
影响因子：
5.3
作者：
Carpenter, MK;Inokuma, MS;Rao, MS
通讯作者：
Rao, MS
影响因子：
5.3
作者：
Keirstead, HS;Nistor, G;Steward, O
通讯作者：
Steward, O
影响因子：
4.2
作者：
Gensel, JC;Tovar, CA;Bresnahan, JC
通讯作者：
Bresnahan, JC
影响因子：
2.7
作者：
Cloutier, Frank;Siegenthaler, Monica M.;Keirstead, Hans S.
通讯作者：
Keirstead, Hans S.