Walker Chandler L, Wang Xiaofei, Bullis Carli, Liu Nai-Kui, Lu Qingbo, Fry Colin, Deng Lingxiao, Xu Xiao-Ming
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Exp Neurol. 2015 Feb;264:163-72. doi: 10.1016/j.expneurol.2014.12.002. Epub 2014 Dec 12.
Schwann cells (SCs) hold promise for spinal cord injury (SCI) repair; however, there are limitations for its use as a lone treatment. We showed that acute inhibition of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) by bisperoxovanadium (bpV) was neuroprotective and enhanced function following cervical hemicontusion SCI. We hypothesized that combining acute bpV therapy and delayed SC engraftment would further improve neuroprotection and recovery after cervical SCI. Adult female Sprague-Dawley (SD) rats were randomly sorted into 5 groups: sham, vehicle, bpV, SC transplantation, and bpV+SC transplantation. SCs were isolated from adult green fluorescent protein (GFP)-expressing SD rats (GFP-SCs). 200 μg/kg bpV(pic) was administered intraperitoneally (IP) twice daily for 7 days post-SCI in bpV-treated groups. GFP-SCs (1×10(6) in 5 μl medium) were transplanted into the lesion epicenter at the 8th day post-SCI. Forelimb function was tested for 10 weeks and histology was assessed. bpV alone significantly reduced lesion (by 40%, p<0.05) and cavitation (by 65%, p<0.05) and improved functional recovery (p<0.05) compared to injury alone. The combination promoted similar neuroprotection (p<0.01 vs. injury); however, GFP-SCs alone did not. Both SC-transplanted groups exhibited remarkable long-term SC survival, SMI-31(+) axon ingrowth and RECA-1(+) vasculature presence in the SC graft; however, bpV+SCs promoted an 89% greater axon-to-lesion ratio than SCs only. We concluded that bpV likely contributed largely to the neuroprotective and functional benefits while SCs facilitated considerable host-tissue interaction and modification. The combination of the two shows promise as an attractive strategy to enhance recovery after SCI.
施万细胞(SCs)有望用于脊髓损伤(SCI)修复;然而,将其作为单一治疗方法存在局限性。我们发现,双过氧钒(bpV)对10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)的急性抑制作用具有神经保护作用,并能增强颈半切损伤性脊髓损伤后的功能。我们推测,将急性bpV治疗与延迟的SCs植入相结合,将进一步改善颈脊髓损伤后的神经保护和恢复。成年雌性Sprague-Dawley(SD)大鼠被随机分为5组:假手术组、溶剂对照组、bpV组、SCs移植组和bpV+SCs移植组。SCs从成年绿色荧光蛋白(GFP)表达的SD大鼠(GFP-SCs)中分离出来。在bpV治疗组中,于脊髓损伤后7天内每天腹腔注射(IP)200μg/kg bpV(pic)两次。在脊髓损伤后第8天,将GFP-SCs(1×10⁶个,置于5μl培养基中)移植到损伤中心。对前肢功能进行了10周的测试,并进行了组织学评估。与单纯损伤相比,单独使用bpV可使损伤显著减少(40%,p<0.05),空洞形成减少(65%,p<0.05),并改善功能恢复(p<0.05)。联合治疗具有相似的神经保护作用(与损伤组相比,p<0.01);然而,单独使用GFP-SCs则没有。两个SCs移植组在SCs移植物中均表现出显著的长期SCs存活、SMI-31(+)轴突长入和RECA-1(+)血管存在;然而,bpV+SCs组的轴突与损伤比例比仅SCs组高8%。我们得出结论,bpV可能在很大程度上促成了神经保护和功能益处,而SCs促进了大量宿主组织的相互作用和改变。两者结合显示出作为增强脊髓损伤后恢复的有吸引力策略的前景。