Kim Hyun Woo, Shi Liang Yu, Lee Min Goo, Kim Ra Hye, Fan Zhi Yi, Koljonen Paul Aarne, Shea Graham Ka Hon
Department of Orthopaedics and Traumatology, LKS Faulty of Medicine, The University of Hong Kong, Hong Kong, China.
Stem Cell Res Ther. 2025 May 28;16(1):262. doi: 10.1186/s13287-025-04348-9.
Degenerative cervical myelopathy (DCM) is the most common disorder affecting the cervical spinal cord in the developed world. Whilst surgery is effective, many patients suffer from residual neurological deficits post-decompression. Cell-based therapies have been studied for traumatic spinal cord injury models but not DCM and may be efficacious as an adjunct to surgical decompression via trophic factor secretion, parenchymal engraftment and/or blood spinal cord barrier reconstitution.
98 SD rats at age 10-12 weeks underwent five weeks of cervical compression by inserting a water-absorbent polyurethane polymer at the C4 epidural space or received sham surgery. Decompression surgery was performed by removing the polymer. Treatment groups received BM-MSCs (bone marrow-derived marrow stromal cells) or BM-neurospheres intravenously or intracisternally at the time of decompression. Locomotor function (BBB testing, rotarod testing, Forelimb Score, and Hind Limb Score) and blood -spinal cord barrier (BSCB) recovery via Evans blue extravasation was observed in 35 rats during the 10-week post-decompression recovery period. 30 rats were used to determine in vivo cell distribution and comparative efficacy of intravenous (IV) or intracisternal (CIS) injection. The remaining rats were sacrificed to assess for the engraftment of transplanted cells. In vivo bioluminescent imaging (BLI) of EGFP-Luciferase BM-MSCs localized cells grossly to organ systems, whilst immunohistochemistry (IHC) of spinal cord specimens targeting anti-human antigens facilitated localization at the site of compression.
BSCB disruption indicated by Evans Blue dye extravasation peaked at Week-4 post-decompression (DW4) and correlated with endoglin expression. Locomotor recovery after polymer removal was delayed with minor improvements observed by Week-8 post-decompression (DW8). IV and CIS injection of BM-MSCs did not lead to significant improvement in locomotor function (p = 0.101, Rotarod Test: PBS vs. CIS) nor of BSCB reconstitution by Day 10 post-decompression. BLI showed significant peripheral organ entrapment of IV BM-MSCs, while CIS BM-MSCs remained in the cervical region, with IHC demonstrating localization to the pia mater. At Day 20, both CIS BM-MSCs and BM-neurospheres similarly failed to significantly improve locomotor function (p = 0.136, Rotarod Test: PBS vs. BM-neurospheres) and transplanted cells were absent from the cervical cord parenchyma.
Human BM-MSCs and BM-neurospheres demonstrate limited efficacy as adjunct therapy to cervical decompression under the present experimental conditions. Adjusting insertable polymer hardness, cell number, and timing of cell transplantation may be future means to demonstrate potential therapeutic effectiveness.
在发达国家，退行性颈椎脊髓病（DCM）是影响颈脊髓的最常见疾病。虽然手术有效，但许多患者在减压后仍存在神经功能缺损。基于细胞的疗法已在创伤性脊髓损伤模型中进行了研究，但尚未用于DCM，并且通过营养因子分泌、实质内植入和/或血脊髓屏障重建，可能作为手术减压的辅助手段有效。
98只10 - 12周龄的SD大鼠，通过在C4硬膜外间隙插入吸水性聚氨酯聚合物进行为期五周的颈椎压迫，或接受假手术。通过移除聚合物进行减压手术。治疗组在减压时经静脉或脑池内给予骨髓间充质干细胞（BM - MSCs）或骨髓神经球。在减压后10周的恢复期内，观察35只大鼠的运动功能（BBB测试、转棒测试、前肢评分和后肢评分）以及通过伊文思蓝外渗评估的血脊髓屏障（BSCB）恢复情况。30只大鼠用于确定静脉注射（IV）或脑池内注射（CIS）的体内细胞分布和比较疗效。其余大鼠处死后评估移植细胞的植入情况。对表达增强绿色荧光蛋白 - 荧光素酶的BM - MSCs进行体内生物发光成像（BLI）可将细胞大致定位到器官系统，而针对抗人抗原的脊髓标本免疫组织化学（IHC）有助于在压迫部位进行定位。
伊文思蓝染料外渗表明的BSCB破坏在减压后第4周（DW4）达到峰值，并与内皮糖蛋白表达相关。移除聚合物后的运动恢复延迟，在减压后第8周（DW8）观察到轻微改善。静脉注射和脑池内注射BM - MSCs在减压后第10天并未导致运动功能有显著改善（p = 0.101，转棒测试：PBS与CIS），也未使BSCB重建。BLI显示静脉注射的BM - MSCs在周围器官有明显滞留，而脑池内注射的BM - MSCs仍留在颈部区域，免疫组织化学显示其定位于软脑膜。在第20天，脑池内注射的BM - MSCs和骨髓神经球同样未能显著改善运动功能（p = 0.136，转棒测试：PBS与骨髓神经球），并且颈髓实质内没有移植细胞。
在当前实验条件下，人BM - MSCs和骨髓神经球作为颈椎减压辅助治疗的疗效有限。调整可插入聚合物的硬度、细胞数量和细胞移植时间可能是未来证明潜在治疗效果的方法。
