Transdifferentiation of bone marrow stromal cells into cholinergic neuronal phenotype: a potential source for cell therapy in spinal cord injury.
OBJECTIVE
Cholinergic neurons are very important cells in spinal cord injuries because of the deficits in motor, autonomic and sensory neurons. In this study, bone marrow stromal cells (BMSC) were evaluated as a source of cholinergic neurons in a rat model of contusive spinal cord injury.


METHODS
BMSC were isolated from adult rats and transdifferentiated into cholinergic neuronal cells. The BMSC were pre-induced with beta-mercaptoethanol (BME), while the induction was done with nerve growth factor (NGF). Neurofilament (NF)-68, -160 and -200 immunostaining was used for evaluating the transdifferentiation of BMSC into a neuronal phenotype. NeuroD expression, a marker for neuroblast differentiation, and Oct-4 expression, a marker for stemness, were evaluated by reverse transcriptase (RT)-polymerase chain reaction (PCR). Choline acetyl transferase (ChAT) immunoreactivity was used for assessing the cholinergic neuronal phenotype. Anti-microtubule-associated protein-2 (MAP-2) and anti-synapsin I antibodies were used as markers for the tendency for synptogenesis. Finally, the induced cells were transplanted into the contused spinal cord and locomotion was evaluated with the Basso-Beattie-Bresnahan (BBB) test.


RESULTS
At the induction stage, there was a decline in the expression of NF-68 associated with a sustained increase in the expression of NF-200, NF-160, ChAT and synapsin I, whereas MAP-2 expression was variable. Transplanted cells were detected 6 weeks after their injection intraspinally and were associated with functional recovery.


CONCLUSIONS
The transdifferentiation of BMSC into a cholinergic phenotype is feasible for replacement therapy in spinal cord injury.
Naghdi
Majid
M
Department of Anatomical Sciences, Tarbiat Modares University, Tehran, Iran.
Tiraihi
Taki
T
Namin
Seyed Alireza Mesbah
SA
Arabkheradmand
Jalil
J
D000818:Animals; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D054338:Cell Transdifferentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000628:therapy*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D016704:Synapsins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D002795:Choline O-Acetyltransferase; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D050810:Octamer Transcription Factors; D016704:Synapsins; C093564:Neurogenic differentiation factor 1