Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine-University Medical Centre Düsseldorf, Moorenstr. 5, 40223 Düsseldorf, Germany.
Brain. 2012 Feb;135(Pt 2):431-46. doi: 10.1093/brain/awr222. Epub 2011 Sep 8.
Stem cell therapy is a potential treatment for spinal cord injury and different stem cell types have been grafted into animal models and humans suffering from spinal trauma. Due to inconsistent results, it is still an important and clinically relevant question which stem cell type will prove to be therapeutically effective. Thus far, stem cells of human sources grafted into spinal cord mostly included barely defined heterogeneous mesenchymal stem cell populations derived from bone marrow or umbilical cord blood. Here, we have transplanted a well-defined unrestricted somatic stem cell isolated from human umbilical cord blood into an acute traumatic spinal cord injury of adult immune suppressed rat. Grafting of unrestricted somatic stem cells into the vicinity of a dorsal hemisection injury at thoracic level eight resulted in hepatocyte growth factor-directed migration and accumulation within the lesion area, reduction in lesion size and augmented tissue sparing, enhanced axon regrowth and significant functional locomotor improvement as revealed by three behavioural tasks (open field Basso-Beattie-Bresnahan locomotor score, horizontal ladder walking test and CatWalk gait analysis). To accomplish the beneficial effects, neither neural differentiation nor long-lasting persistence of the grafted human stem cells appears to be required. The secretion of neurite outgrowth-promoting factors in vitro further suggests a paracrine function of unrestricted somatic stem cells in spinal cord injury. Given the highly supportive functional characteristics in spinal cord injury, production in virtually unlimited quantities at GMP grade and lack of ethical concerns, unrestricted somatic stem cells appear to be a highly suitable human stem cell source for clinical application in central nervous system injuries.
干细胞疗法是脊髓损伤的一种潜在治疗方法，不同类型的干细胞已被移植到动物模型和患有脊髓创伤的人类中。由于结果不一致，哪种干细胞类型将被证明具有治疗效果仍然是一个重要且具有临床相关性的问题。到目前为止，移植到脊髓中的人类来源的干细胞大多包括从骨髓或脐血中获得的定义不明确的异质性间充质干细胞群体。在这里，我们将一种从人脐血中分离出来的定义明确的无限制体干细胞移植到成年免疫抑制大鼠的急性创伤性脊髓损伤中。将无限制体干细胞移植到胸 8 水平的背侧半切损伤附近，导致肝细胞生长因子定向迁移和在损伤区域内积聚，减少损伤大小和增加组织保留，增强轴突再生，并通过三项行为任务（开阔场 Basso-Beattie-Bresnahan 运动评分、水平梯行走测试和 CatWalk 步态分析）显著改善功能运动能力。为了实现有益效果，移植的人类干细胞既不需要神经分化，也不需要长期持续存在。体外的神经突生长促进因子的分泌进一步表明无限制体干细胞在脊髓损伤中的旁分泌功能。鉴于在脊髓损伤中具有高度支持性功能特征、以 GMP 级大量生产以及没有伦理问题，无限制体干细胞似乎是一种非常适合用于中枢神经系统损伤的临床应用的人类干细胞来源。
