中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (6): 1046-1053.doi: 10.4103/1673-5374.233448

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

静脉或腹腔注射骨髓间充质干细胞：谁更利于脊髓损伤后的修复？

  

  • 收稿日期:2018-04-11 出版日期:2018-06-15 发布日期:2018-06-15

 Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

Bruna dos Santos Ramalho, Fernanda Martins de Almeida, Conrado Mendonça Sales, Silmara de Lima, Ana Maria Blanco Martinez   

  1. Laboratório de Neurodegeneração e Reparo, Departamento de Patologia – Faculdade de Medicina, HUCFF, Universidade Federal do Rio de
    Janeiro, Rio de Janeiro, Brazil
  • Received:2018-04-11 Online:2018-06-15 Published:2018-06-15
  • Contact: Ana Maria Blanco Martinez,M.D., Ph.D.,anamartinez@hucff.ufrj.br.

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摘要：

细胞移植治疗脊髓损伤的给药途径对于临床应用非常重要，因为直接注射到受损脊髓中可能会导致进一步损伤。因而实验设计观察静脉或腹腔注射移植骨髓间充质干细胞（MSCs）对压迫性脊髓损伤小鼠模型的干预效果。实验用血管夹压迫成年C57BL/6小鼠T9脊髓1min建立压迫性脊髓损伤小鼠模型，然后于损伤后7 d接受腹腔或静脉注射8×105个骨髓间充质干细胞，并以腹腔或静脉注射DMEM培养基为对照。用Luxol fast blue染色法分析小鼠脊髓白质保留情况。在用甲苯胺蓝染色的计数脊髓存留的神经纤维数量，并通过免疫组织化学分析神经营养因子的存在。同时，用Basso 小鼠量表和总体运动能力测试分析了小鼠的运动表现。结果显示接受腹腔或静脉注射骨髓间充质干细胞的小鼠脊髓白质和神经纤维保留量比注射DMEM培养基的小鼠多，且脊髓中神经营养因子脑源性神经营养因子、神经生长因子、神经营养素3和神经营养素4表达水平更高，运动功能也明显改善；且两种细胞移植干预结果相近。作者认为，腹腔或静脉注射两种骨髓间充质干细胞移植途径干预压迫性脊髓损伤均可产生有益的结果。

orcid:0000-0002-0821-5730(Ana Maria Blanco Martinez)

关键词: 脊髓损伤, 骨髓间充质干细胞, 静脉途径, 腹腔内途径, 功能恢复, 干细胞, 神经再生

Abstract:

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury (SCI) are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells (MSCs) in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups:sham (anesthesia and laminectomy but without compression injury induction), MSC i.p. (intraperitoneal injection of 8 × 105 MSCs in 500 μL of DMEM at 7 days after SCI), MSC i.v. (intravenous injection of 8× 105 MSCs in 500 μL of DMEM at 7 days after SCI), DMEM i.p. (intraperitoneal injection of 500 μL of DMEM at 7 days after SCI), DMEM i.v. (intravenous injection of 500 μL of DMEM at 7 days after SCI). The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors (brain-derived neurotrophic factor, nerve growth factor,neurotrophin-3 and neurotrophin-4) in the spinal cord and improved locomotor performance. Our results indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial outcomes and can be elected as a choice for SCI treatment.

Key words: spinal cord injury, mesenchymal stem cells, intravenous route, intraperitoneal route, functional recovery, systemic transplantation, neural regeneration