期刊
ANNALS OF NEUROLOGY
卷 60, 期 1, 页码 32-44出版社
WILEY
DOI: 10.1002/ana.20901
关键词
-
资金
- NINDS NIH HHS [R01 NS50412-01] Funding Source: Medline
Objective: We explored the potential of embryonic stem cell-derived motor neurons to functionally replace those cells destroyed in paralyzed adult rats. Methods: 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. Results: 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. Interpretation: 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.
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