TY - JOUR
T1 - Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice
AU - Micci, Maria Adelaide
AU - Kahrig, Kristen M.
AU - Simmons, Rochelle S.
AU - Sarna, Sushil K.
AU - Espejo-Navarro, M. Rosario
AU - Pasricha, Pankaj Jay
PY - 2005/12
Y1 - 2005/12
N2 - Background & Aims: Nitric oxide is a major inhibitory neurotransmitter in the enteric nervous system. Loss or dysfunction of nitrinergic neurons is associated with serious disruptions of motility, intractable symptoms, and long-term suffering. The aim of this study was to evaluate the effect of intrapyloric transplantation of neural stem cells (NSCs) on gastric emptying and pyloric function in nNOS-/- mice, a well-established genetic model of gastroparesis. Methods: NSCs were isolated from embryonic mice transgenically engineered to express green fluorescent protein and transplanted into the pylorus of nNOS-/- mice. Grafted cells were visualized in pyloric sections and further characterized by immunofluorescence staining. One week posttransplantation, gastric emptying to a non-nutrient meal was measured using the phenol red method and pyloric function was assessed by measuring the relaxation of pyloric strips in an organ bath in response to electrical field stimulation (EFS) under nonadrenergic, noncholinergic conditions. Results: One week following implantation, grafted NSCs differentiated into neurons and expressed neuronal nitric oxide synthase. Gastric emptying was significantly increased in mice that received NSCs as compared with vehicle-injected controls (49.67% vs 35.09%; P < .01 by Student t test). EFS-induced relaxation of pyloric strips was also significantly increased (P < .01 by 2-way analysis of variance). The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester and the neuronal blocker tetrodotoxin blocked the EFS-induced relaxation, indicating that the observed effect is NO mediated and neuronally derived. Conclusions: Our results support the potential of NSC transplantation as a viable therapeutic option for neuroenteric disorders.
AB - Background & Aims: Nitric oxide is a major inhibitory neurotransmitter in the enteric nervous system. Loss or dysfunction of nitrinergic neurons is associated with serious disruptions of motility, intractable symptoms, and long-term suffering. The aim of this study was to evaluate the effect of intrapyloric transplantation of neural stem cells (NSCs) on gastric emptying and pyloric function in nNOS-/- mice, a well-established genetic model of gastroparesis. Methods: NSCs were isolated from embryonic mice transgenically engineered to express green fluorescent protein and transplanted into the pylorus of nNOS-/- mice. Grafted cells were visualized in pyloric sections and further characterized by immunofluorescence staining. One week posttransplantation, gastric emptying to a non-nutrient meal was measured using the phenol red method and pyloric function was assessed by measuring the relaxation of pyloric strips in an organ bath in response to electrical field stimulation (EFS) under nonadrenergic, noncholinergic conditions. Results: One week following implantation, grafted NSCs differentiated into neurons and expressed neuronal nitric oxide synthase. Gastric emptying was significantly increased in mice that received NSCs as compared with vehicle-injected controls (49.67% vs 35.09%; P < .01 by Student t test). EFS-induced relaxation of pyloric strips was also significantly increased (P < .01 by 2-way analysis of variance). The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester and the neuronal blocker tetrodotoxin blocked the EFS-induced relaxation, indicating that the observed effect is NO mediated and neuronally derived. Conclusions: Our results support the potential of NSC transplantation as a viable therapeutic option for neuroenteric disorders.
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U2 - 10.1053/j.gastro.2005.08.055
DO - 10.1053/j.gastro.2005.08.055
M3 - Article
C2 - 16344050
AN - SCOPUS:28844451418
SN - 0016-5085
VL - 129
SP - 1817
EP - 1824
JO - Gastroenterology
JF - Gastroenterology
IS - 6
ER -