Deshpande Deepa M, Kim Yun-Sook, Martinez Tara, Carmen Jessica, Dike Sonny, Shats Irina, Rubin Lee L, Drummond Jennifer, Krishnan Chitra, Hoke Ahmet, Maragakis Nicholas, Shefner Jeremy, Rothstein Jeffrey D, Kerr Douglas A
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-6965, USA.
Ann Neurol. 2006 Jul;60(1):32-44. doi: 10.1002/ana.20901.
We explored the potential of embryonic stem cell-derived motor neurons to functionally replace those cells destroyed in paralyzed adult rats.
We administered a phosphodiesterase type 4 inhibitor and dibutyryl cyclic adenosine monophosphate to overcome myelin-mediated repulsion and provided glial cell-derived neurotrophic factor within the sciatic nerve to attract transplanted embryonic stem cell-derived axons toward skeletal muscle targets.
We found that these strategies significantly increased the success of transplanted axons extending out of the spinal cord into ventral roots. Furthermore, transplant-derived axons reached muscle, formed neuromuscular junctions, were physiologically active, and mediated partial recovery from paralysis.
We conclude that restoration of functional motor units by embryonic stem cells is possible and represents a potential therapeutic strategy for patients with paralysis. To our knowledge, this is the first report of the anatomical and functional replacement of a motor neuron circuit within the adult mammalian host.
我们探讨了胚胎干细胞衍生的运动神经元在功能上替代成年瘫痪大鼠体内被破坏细胞的潜力。
我们给予一种4型磷酸二酯酶抑制剂和二丁酰环磷酸腺苷以克服髓磷脂介导的排斥作用，并在坐骨神经内提供胶质细胞源性神经营养因子，以吸引移植的胚胎干细胞衍生的轴突朝向骨骼肌靶标。
我们发现这些策略显著提高了移植轴突从脊髓延伸至腹根的成功率。此外，移植衍生的轴突到达肌肉，形成神经肌肉接头，具有生理活性，并介导了瘫痪的部分恢复。
我们得出结论，胚胎干细胞恢复功能性运动单位是可能的，这代表了一种针对瘫痪患者的潜在治疗策略。据我们所知，这是成年哺乳动物宿主体内运动神经元回路进行解剖学和功能替代的首次报道。
