Sarveazad Arash, Babahajian Asrin, Bakhtiari Mehrdad, Soleimani Mansoureh, Behnam Babak, Yari Abazar, Akbari Abolfazl, Yousefifard Mahmoud, Janzadeh Atousa, Amini Naser, Agah Shahram, Fallah Ali, Joghataei Mohammad Taghi
Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Liver & Digestive Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Neuropeptides. 2017 Feb;61:39-47. doi: 10.1016/j.npep.2016.07.004. Epub 2016 Jul 28.
Although stem cell therapy has become a major focus as a new option for management of spinal cord injury (SCI), its effectiveness should be promoted. In this study, we investigated the effects of co-administrating human adipose-derived stem cells (hADSCs) and Chondroitinase ABC (ChABC) in a rat model of spinal cord injury.
hADSCs derived from superficial layer of abdominal adipose tissue were used to treat a contusion-induced SCI. Animals were randomly allocated to five equal groups including sham (only laminectomy), SCI (SCI+vehicle injection), hADSCs (1×10⁶ hADSCs/10μl intra-spinal injection), ChABC (10μl of 100U/ml ChABC intra-spinal injection injection), and hADSCs+ChABC. Basso, Beattie and Bresnahan tests were used to evaluate locomotor function. 8weeks after treatment, cavity size, myelination, cell differentiation (neuron and astrocyte), and chondroitin sulfate amount were analyzed.
hADSC transplanted animals, ChABC injected animals (P<0.001), and hADSC+ChABC treated rats (P<0.001) displayed significant motor improvement compared to SCI group. Combination therapy of hADSCs and ChABC led to greater locomotor recovery compared to using hADSCs (P<0.001) or ChABC (P<0.01) alone. Spinal cords in the combined and single therapy groups had cavities filled with myelinated areas and less chondroitin sulfate content in comparison with the control group (P<0.001). hADSCs expressed GFAP, B III tubulin and Map2.
Combination therapy with ChABC and hADSCs exhibits more significant functional recovery than single therapy using either. This result may be applicable in selection of the best therapeutic strategy for SCI.
尽管干细胞疗法已成为脊髓损伤(SCI)治疗新选择的主要焦点,但其有效性仍有待提高。在本研究中,我们在大鼠脊髓损伤模型中研究了联合给予人脂肪来源干细胞(hADSCs)和软骨素酶ABC(ChABC)的效果。
使用从腹部脂肪组织表层获取的hADSCs治疗挫伤诱导的SCI。动物被随机分为五组,每组数量相等,包括假手术组(仅行椎板切除术)、SCI组(SCI + 注射赋形剂)、hADSCs组(1×10⁶个hADSCs/10μl脊髓内注射)、ChABC组(10μl 100U/ml ChABC脊髓内注射)和hADSCs + ChABC组。使用Basso、Beattie和Bresnahan测试评估运动功能。治疗8周后,分析空洞大小、髓鞘形成、细胞分化(神经元和星形胶质细胞)以及硫酸软骨素含量。
与SCI组相比,hADSC移植动物、ChABC注射动物(P<0.001)和hADSC + ChABC治疗大鼠(P<0.001)的运动功能有显著改善。与单独使用hADSCs(P<0.001)或ChABC(P<0.01)相比,hADSCs和ChABC联合治疗导致更大程度的运动恢复。与对照组相比,联合治疗组和单一治疗组的脊髓空洞内充满有髓鞘区域,硫酸软骨素含量较低(P<0.001)。hADSCs表达胶质纤维酸性蛋白(GFAP)、βIII微管蛋白和微管相关蛋白2(Map2)。
ChABC和hADSCs联合治疗比单独使用单一疗法表现出更显著的功能恢复。这一结果可能适用于选择SCI的最佳治疗策略。