Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Cytotherapy. 2012 May;14(5):584-97. doi: 10.3109/14653249.2012.658913. Epub 2012 Feb 21.
Previous studies have reported that scaffold or cell-based transplantation may improve functional recovery following spinal cord injury (SCI), but these results were based on neuronal regeneration and cell replacement. In this study, we investigated whether a combination of Matrigel and neural-induced mesenchymal stem cells (NMSC) improved hindlimb function in dogs with SCI, and what mechanisms were involved.
We pre-differentiated canine adipose-derived mesenchymal stem cells into NMSC. A total of 12 dogs subjected to SCI procedures were assigned to one of the following three transplantation treatment groups: phosphate-buffered saline (PBS); Matrigel; or Matrigel seeded with NMSC. Treatment occurred 1 week after SCI. Basso, Beattie and Bresnahan (B.B.B.) and Tarlov scores, histopathology, immunofluorescence staining and Western blot analysis were used to evaluate the treatment effects.
Compared with dogs administered PBS or Matrigel alone, dogs treated with Matrigel + NMSC showed significantly better functional recovery 8 weeks after transplantation. Histology and immunochemical analysis revealed that the combination of Matrigel + NMSC reduced fibrosis from secondary injury processes and improved neuronal regeneration more than the other treatments. In addition, the combination of Matrigel + NMSC decreased the expression of inflammation and/or astrogliosis markers. Increased expressions of intracellular molecules related to neuronal extension, neuronal markers and neurotrophic factors were also found in the Matrigel + NMSC group. However, the expression of nestin as a neural stem cell marker was increased with Matrigel alone.
The combination of Matrigel + NMSC produced beneficial effects in dogs with regard to functional recovery following SCI through enhancement of anti-inflammation, anti-astrogliosis, neuronal extension and neuronal regeneration effects.
先前的研究报告称，支架或细胞移植可能改善脊髓损伤（SCI）后的功能恢复，但这些结果基于神经元再生和细胞替代。在本研究中，我们研究了 Matrigel 和神经诱导间充质干细胞（NMSC）的组合是否改善犬 SCI 后的后肢功能，以及涉及哪些机制。
我们将犬脂肪间充质干细胞预先分化为 NMSC。共有 12 只犬接受 SCI 手术，分为以下三种移植治疗组之一：磷酸盐缓冲液（PBS）；Matrigel；或 Matrigel 接种 NMSC。治疗在 SCI 后 1 周进行。Basso、Beattie 和 Bresnahan（B.B.B.）和 Tarlov 评分、组织病理学、免疫荧光染色和 Western blot 分析用于评估治疗效果。
与单独给予 PBS 或 Matrigel 的犬相比，给予 Matrigel+NMSC 的犬在移植后 8 周时功能恢复明显更好。组织学和免疫化学分析显示，Matrigel+NMSC 组合减少了继发性损伤过程中的纤维化，并比其他治疗方法更好地促进了神经元再生。此外，Matrigel+NMSC 组合降低了炎症和/或星形胶质细胞标志物的表达。还发现 Matrigel+NMSC 组中与神经元延伸、神经元标志物和神经营养因子相关的细胞内分子表达增加。然而，单独使用 Matrigel 时，神经干细胞标志物 nestin 的表达增加。
Matrigel+NMSC 的组合通过增强抗炎、抗星形胶质细胞、神经元延伸和神经元再生作用，对犬 SCI 后的功能恢复产生有益影响。
