Hofstetter C P, Schwarz E J, Hess D, Widenfalk J, El Manira A, Prockop Darwin J, Olson L
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2199-204. doi: 10.1073/pnas.042678299.
Marrow stromal cells (MSC) can be expanded rapidly in vitro and differentiated into multiple mesodermal cell types. In addition, differentiation into neuron-like cells expressing markers typical for mature neurons has been reported. To analyze whether such cells, exposed to differentiation media, could develop electrophysiological properties characteristic of neurons, we performed whole-cell recordings. Neuron-like MSC, however, lacked voltage-gated ion channels necessary for generation of action potentials. We then delivered MSC into the injured spinal cord to study the fate of transplanted MSC and possible effects on functional outcome in animals rendered paraplegic. MSC given 1 week after injury led to significantly larger numbers of surviving cells than immediate treatment and significant improvements of gait. Histology 5 weeks after spinal cord injury revealed that MSC were tightly associated with longitudinally arranged immature astrocytes and formed bundles bridging the epicenter of the injury. Robust bundles of neurofilament-positive fibers and some 5-hydroxytryptamine-positive fibers were found mainly at the interface between graft and scar tissue. MSC constitute an easily accessible, easily expandable source of cells that may prove useful in the establishment of spinal cord repair protocols.
骨髓基质细胞(MSC)可在体外快速扩增并分化为多种中胚层细胞类型。此外,已有报道称其可分化为表达成熟神经元典型标志物的神经元样细胞。为分析暴露于分化培养基中的此类细胞是否能发育出神经元特有的电生理特性,我们进行了全细胞记录。然而,神经元样MSC缺乏产生动作电位所需的电压门控离子通道。然后,我们将MSC移植到受损脊髓中,以研究移植的MSC的命运以及对截瘫动物功能结局的可能影响。损伤后1周给予MSC比立即治疗导致存活细胞数量显著增多,且步态有显著改善。脊髓损伤5周后的组织学检查显示,MSC与纵向排列的未成熟星形胶质细胞紧密相连,并形成束状结构跨越损伤中心。主要在移植物与瘢痕组织的界面处发现了粗壮的神经丝阳性纤维束和一些5-羟色胺阳性纤维。MSC构成了一种易于获取、易于扩增的细胞来源,可能在脊髓修复方案的制定中证明是有用的。