Membrane properties of neuron-like cells generated from adult human bone-marrow-derived mesenchymal stem cells.
Adult mesenchymal stem cells (MeSCs) isolated from human bone marrow are capable of generating neural stem cell (NSC)-like cells that can be subsequently differentiated into cells expressing molecular markers for neurons. Here we report that these neuron-like cells had functional properties similar to those of brain-derived neurons. Whole-cell patch-clamp recordings and calcium imaging experiments were performed on neuron-like cells differentiated from bone-marrow-derived NSC-like cells. The neuron-like cells were subjected to current pulses to determine if they were capable of generating depolarization-induced action potentials. We found that nearly all of the cells with neuron-like morphology exhibited active membrane properties in response to the depolarizing pulses. The most common response was a single spike-like event with an overshoot and brief afterhyperpolarization. Cells that did not generate overshooting spike-like events usually displayed rectifying current-voltage relationships. The prevalence of these active membrane properties in response to the depolarizing current pulses suggested that the human MeSCs (hMeSCs) were capable of converting to a neural lineage under defined culture conditions. The spike-like events were blocked by the voltage-gated sodium channel inhibitor lidocaine, but unaffected by another sodium channel inhibitor tetrodotoxin (TTX). In calcium imaging experiments, the neuron-like cells responded to potassium chloride depolarization and l-glutamate application with increases in the cytoplasmic calcium levels. Thus, the neuron-like cells appeared to express TTX-resistant voltage-gated sodium channels, voltage-gated calcium channels, and functional l-glutamate receptors. These results demonstrate that hMeSCs were capable of generating cells with characteristics typical of functional neurons that may prove useful for neuroreplacement therapies.
Fox
Lyle E
LE
Department of Pain Management, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Shen
Jun
J
Ma
Ke
K
Liu
Qing
Q
Shi
Guangbin
G
Pappas
George D
GD
Qu
Tingyu
T
Cheng
Jianguo
J
D000200:Action Potentials / Q000187:drug effects; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000032:analysis; D015220:Calcium Channels / Q000502:physiology; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D008566:Membranes; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D015415:Biomarkers; D015220:Calcium Channels; D024642:Potassium Channels, Voltage-Gated; D017470:Receptors, Glutamate; D015222:Sodium Channels; D013779:Tetrodotoxin; D011189:Potassium Chloride; D008012:Lidocaine; D002118:Calcium
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