Amarna Therapeutics, Leiden, The Netherlands.
J Neural Transm (Vienna). 2013 Jan;120(1):91-102. doi: 10.1007/s00702-012-0868-x. Epub 2012 Jul 29.
Ischemic and traumatic insults of the central nervous system both result in definite chronic disability, only to some extent responsive to rehabilitation. Recently, the application of autologous stem cells (fresh bone marrow-derived mononuclear cells including mesenchymal and hematopoietic stem cells) was suggested to provide a strategy to further improve neurological recovery in these disorders. During the acute phase, stem cells act mainly by neuroprotection with prevention of apoptosis, whereas during the chronic situation they provide neurorestoration by transdifferentiation and/or the secretion of neurotrophic factors. To reach these goals, in the acute phase, stem cells (10 million mononuclear cells per kg body weight) might be best applied intravenously, as during the first 7 days after the lesion, the blood-brain barrier permits passage of cells from the blood into the brain or the spinal cord. In the more chronic situation, though, those cells might be applied best intrathecally by lumbar puncture. Based on the reported results so far, it seems justified to develop well-designed clinical double-blind trials in chronic spinal cord injury and ischemic stroke patients, as efficacy and safety concerns might not be answered by preclinical studies.
中枢神经系统的缺血性和外伤性损伤都会导致明确的慢性残疾，仅在一定程度上对康复治疗有反应。最近，自体干细胞（包括间充质和造血干细胞的新鲜骨髓源性单核细胞）的应用被认为是提供进一步改善这些疾病神经恢复的一种策略。在急性期，干细胞主要通过神经保护作用来预防细胞凋亡，而在慢性期，它们通过转分化和/或分泌神经营养因子来提供神经修复。为了达到这些目标，在急性期，干细胞（每公斤体重 1000 万个单核细胞）最好通过静脉内给药，因为在损伤后的前 7 天内，血脑屏障允许细胞从血液进入大脑或脊髓。然而，在更慢性的情况下，这些细胞可能通过腰椎穿刺最好通过鞘内给药。基于迄今为止的报告结果，似乎有理由在慢性脊髓损伤和缺血性中风患者中开展精心设计的临床双盲试验，因为临床前研究可能无法回答疗效和安全性问题。
