Comparison of functional and histological outcomes after intralesional, intracisternal, and intravenous transplantation of human bone marrow-derived mesenchymal stromal cells in a rat model of spinal cord injury
Comparison of functional and histological outcomes after intralesional, intracisternal, and intravenous transplantation of human bone marrow-derived mesenchymal stromal cells in a rat model of spinal cord injury
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DOI：
10.1007/s00701-013-1799-5
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发表时间：
2013-10-01
影响因子：
2.4
通讯作者：
Kim, Keung Nyun
中科院分区：
文献类型：
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作者：
Shin, Dong Ah;Kim, Jin-Myung;Kim, Keung Nyun
很少有研究比较干细胞移植的方法。本研究的目的是确定治疗脊髓损伤(SCI)的最佳干细胞输送方法。我们比较了通过病灶内(ILT)、脑池内(ICT)和静脉移植(IVT)移植人骨髓基质细胞(BMSCs)后的功能和组织学结果。从25 mm的高度将直径2 mm的10g重量滴在动物暴露的脊髓上，建立了大鼠脊髓损伤模型。在每个治疗组中，随机分配24只动物进行功能评估，24只进行组织学检查。骨髓间充质干细胞(3×10(5)，ILT；1×10(6)，ICT；2×10(6)，IVT)在脊髓损伤后1周移植。每周对所有动物进行Basso-Beattie-Bresnahan评分，连续6周。脊髓损伤后2、4、6周每组各取8只动物的脊髓标本。在每个脊髓的6个矢状面切片上计数存活的BMSCs。从干细胞注射后2周开始，所有三个治疗组与对照组相比，功能恢复均有改善(P<；0.01)。ICT组功能恢复最佳，ILT组次之，IVT组次之(P<；0.01)。组织学分析显示，ILT组存活的BMSCs数量最多，其次是ICT组和IVT组(P<；0.01)。如果不限制移植细胞的数量，ICT可能是运送干细胞和改善脊髓损伤患者功能结局的最安全和最有效的方法。随着提高植入率的研究的进展，功能结果的进一步改善是可以预期的。
Few studies have compared methods of stem cell transplantation. The aim of the present study was to determine the optimal method of delivery of therapeutic stem cells in spinal cord injury (SCI). We compared functional and histologic outcomes after administration of human bone marrow stromal cells (BMSCs) by intralesional (ILT), intracisternal (ICT), and intravenous transplantation (IVT).A rat model of spinal cord injury was produced by dropping a 10-g weight, 2 mm in diameter, onto the exposed spinal cords of animals from a height of 25 mm. In each treatment group, 24 animals were randomly assigned for functional assessment and 24 for histologic examination. BMSCs (3 x 10(5), ILT; 1 x 10(6), ICT; 2 x 10(6), IVT) were transplanted 1 week after SCI in numbers determined in previous studies. Basso-Beattie-Bresnahan scoring was performed in all animals weekly for 6 weeks. Spinal cord specimens were obtained from eight animals in each group 2, 4, and 6 weeks after SCI. Viable BMSCs were counted in six sagittal sections from each spinal cord.All three treatment groups showed improved functional recovery compared to controls beginning 2 weeks after stem cell injection (P < 0.01). The ICT group showed the best functional recovery, followed by the ILT and IVT groups, respectively (P < 0.01). Histological analysis showed the largest number of viable BMSCs in the ILT group, followed by the ICT and IVT groups, respectively (P < 0.01).ICT may be the safest and most effective method for delivering stem cells and improving functional outcome in SCI when no limits are placed on the number of cells transplanted. As research on enhancing engraftment rates advances, further improvement of functional outcome can be expected.