Cízková Dasa, Rosocha Ján, Vanický Ivo, Jergová Stanislava, Cízek Milan
Institute of Neurobiology, Center of Excellence, SAS, Soltésovej 4, Kosice, 04001, Slovakia.
Cell Mol Neurobiol. 2006 Oct-Nov;26(7-8):1167-80. doi: 10.1007/s10571-006-9093-1. Epub 2006 Jul 29.
Human mesenchymal stem cells (hMSCs) derived from adult bone marrow represent a potentially useful source of cells for cell replacement therapy after nervous tissue damage. They can be expanded in culture and reintroduced into patients as autografts or allografts with unique immunologic properties. The aim of the present study was to investigate (i) survival, migration, differentiation properties of hMSCs transplanted into non-immunosuppressed rats after spinal cord injury (SCI) and (ii) impact of hMSC transplantation on functional recovery. Seven days after SCI, rats received i.v. injection of hMSCs (2x10(6) in 0.5 mL DMEM) isolated from adult healthy donors. Functional recovery was assessed by Basso-Beattie-Bresnahan (BBB) score weekly for 28 days. Our results showed gradual improvement of locomotor function in transplanted rats with statistically significant differences at 21 and 28 days. Immunocytochemical analysis using human nuclei (NUMA) and BrdU antibodies confirmed survival and migration of hMSCs into the injury site. Transplanted cells were found to infiltrate mainly into the ventrolateral white matter tracts, spreading also to adjacent segments located rostro-caudaly to the injury epicenter. In double-stained preparations, hMSCs were found to differentiate into oligodendrocytes (APC), but not into cells expressing neuronal markers (NeuN). Accumulation of GAP-43 regrowing axons within damaged white matter tracts after transplantation was observed. Our findings indicate that hMSCs may facilitate recovery from spinal cord injury by remyelinating spared white matter tracts and/or by enhancing axonal growth. In addition, low immunogenicity of hMSCs was confirmed by survival of donor cells without immunosuppressive treatment.
源自成人骨髓的人间充质干细胞（hMSCs）是神经组织损伤后细胞替代治疗中一种潜在有用的细胞来源。它们可以在培养中扩增，并作为具有独特免疫特性的自体移植物或同种异体移植物重新引入患者体内。本研究的目的是调查：（i）脊髓损伤（SCI）后移植到未免疫抑制大鼠体内的hMSCs的存活、迁移和分化特性；（ii）hMSC移植对功能恢复的影响。SCI后7天，大鼠接受静脉注射从成年健康供体分离的hMSCs（0.5 mL DMEM中含2x10(6)个细胞）。每周用Basso-Beattie-Bresnahan（BBB）评分评估功能恢复情况，持续28天。我们的结果显示，移植大鼠的运动功能逐渐改善，在第21天和第28天有统计学显著差异。使用人细胞核（NUMA）和BrdU抗体的免疫细胞化学分析证实了hMSCs在损伤部位的存活和迁移。发现移植细胞主要浸润到腹外侧白质束，也扩散到损伤中心头端至尾端相邻节段。在双重染色制剂中，发现hMSCs分化为少突胶质细胞（APC），但未分化为表达神经元标志物（NeuN）的细胞。观察到移植后受损白质束内GAP-43再生轴突的积累。我们的研究结果表明，hMSCs可能通过对 spared白质束进行髓鞘再生和/或通过增强轴突生长来促进脊髓损伤的恢复。此外，hMSCs的低免疫原性通过未进行免疫抑制治疗时供体细胞的存活得到证实。
