Department of Orthopedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Spine (Phila Pa 1976). 2013 Aug 1;38(17):E1065-74. doi: 10.1097/BRS.0b013e31829839fa.
Animal experimental study.
To present experimental evidence for mesenchymal cell therapy for spinal cord injury (SCI).
Prior to clinical application of stem cell therapy for SCI, many critical issues have to be addressed including efficiency, safety, method of transplantation, and differentiation of the transplanted cells.
Chronic contusive SCI was induced in 36 Sprague-Dawley rats and randomly assigned to the intralesional (IL), intravenous (IV), or control groups. At 6 weeks post injury, allogenic mesenchymal stem cells (MSCs, 1 × 10 cells) were transplanted either intralesionally or intravenously for the intervention groups. Engraftment of the transplanted MSCs was evaluated with PKH 26 staining. Differentiation was evaluated using double stain with neuronal and glial cell markers. Brain-derived neurotrophic factor and nerve growth factor (NGF) were used for neurotrophic factor expression. Basso, Beattie, and Bresnahan locomotor rating scale was used for evaluation of functional recovery.
The estimated engraftment percentage of the transplanted cells in the IL group and IV group were 36.5%, and 15.5%, respectively. The engraftment of the transplanted MSCs was higher in the IL group than in the IV group. Most of the transplanted MSCs were colocalized with GFAP in both transplantation groups. Brain-derived neurotrophic factor and NGF expression (Western blot and real-time polymerase chain reaction) in the injured spinal cord was higher in both transplanted groups compared with those in the control group. At 6 weeks post transplantation, the mean Basso, Beattie, and Bresnahan locomotor scales in the IL, IV, and control groups were 5.63 ± 0.89, 5.63 ± 1.03, and 2.88 ± 0.44, respectively. The functional recovery seen in the rats that underwent transplantation was significantly better than that in the control group (P < 0.05).
Although the number of engrafted cells and expression of neurotrophic factors were lower in the IV group than those in the IL group, both IL and IV transplantation of MSC in the chronic SCI gave a significant clinical improvement. However, there were no differences in differentiation of the transplanted cells between the IL group and IV group. Astrocytic differentiation of the transplanted cells was predominant.
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动物实验研究。
为脊髓损伤（SCI）的间充质细胞治疗提供实验依据。
在将干细胞疗法应用于 SCI 之前，必须解决许多关键问题，包括效率、安全性、移植方法和移植细胞的分化。
将 36 只 Sprague-Dawley 大鼠诱导为慢性挫伤性 SCI，并随机分为损伤内（IL）、静脉内（IV）或对照组。在损伤后 6 周，所有异体间充质干细胞（MSCs，1×10 个细胞）分别经损伤内或静脉内移植干预组。通过 PKH26 染色评估移植 MSC 的植入情况。通过神经元和神经胶质细胞标志物的双重染色评估分化。使用脑源性神经营养因子和神经生长因子（NGF）来评估神经营养因子的表达。使用 Basso、Beattie 和 Bresnahan 运动评分量表评估功能恢复情况。
IL 组和 IV 组移植细胞的估计植入率分别为 36.5%和 15.5%。IL 组移植 MSC 的植入率高于 IV 组。在这两个移植组中，大多数移植的 MSC 与 GFAP 共定位。与对照组相比，在两个移植组中，损伤脊髓中的脑源性神经营养因子和 NGF 表达（Western blot 和实时聚合酶链反应）均较高。在移植后 6 周，IL、IV 和对照组的平均 Basso、Beattie 和 Bresnahan 运动评分分别为 5.63±0.89、5.63±1.03 和 2.88±0.44。接受移植的大鼠的功能恢复明显优于对照组（P<0.05）。
尽管 IV 组的植入细胞数量和神经营养因子的表达低于 IL 组，但慢性 SCI 中 IL 和 IV 移植 MSC 均显著改善了临床效果。然而，IL 组和 IV 组之间移植细胞的分化没有差异。移植细胞以星形胶质细胞分化为主。
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