Cholinergic Neuron-Like Cells Derived from Bone Marrow Stromal Cells Induced by Tricyclodecane-9-yl-Xanthogenate Promote Functional Recovery and Neural Protection after Spinal Cord Injury

• Published in: Cell transplantation Vol. 22; no. 6; pp. 961 - 975
• Main Authors: Sun, Chunhui, Shao, Jing, Su, Le, Zhao, Jing, Bi, Jianzhong, Yang, Shaonan, Zhang, Shangli, Gao, Jiangang, Miao, Junying
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2013; SAGE Publishing
• Subjects: Acetylcholine - metabolism; Animals; Axons - drug effects; Biomarkers - metabolism; Bridged-Ring Compounds - pharmacology; Bromodeoxyuridine - metabolism; Cell Differentiation - drug effects; Choline O-Acetyltransferase - metabolism; Cholinergic Neurons - cytology; Cholinergic Neurons - enzymology; Cholinergic Neurons - transplantation; Glutamate Decarboxylase - metabolism; Graft Rejection - immunology; Immunohistochemistry; Male; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - enzymology; Mice; Mice, Inbred C57BL; Motor Neurons - cytology; Motor Neurons - drug effects; Motor Neurons - metabolism; Nerve Regeneration - drug effects; Neuroprotective Agents - pharmacology; Rats; Recovery of Function - drug effects; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Thiones - pharmacology; Transplantation, Heterologous; Cell transplantation; Spinal cord injury (SCI); Bone marrow stromal cells (BMSCs); Cholinergic neuron differentiation; Tricyclodecane-9-yl-xanthogenate (D609)
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/096368912X657413

The rate of neuronal differentiation of bone marrow stromal cells (BMSCs) in vivo is very low; therefore, it is necessary to elevate the number of BMSC-derived neurons to cure neurodegenerative diseases. We previously reported that tricyclodecane-9-yl-xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), induced BMSCs to differentiate into neuron-like cells in vitro. However, the neuronal type is not clear, and it is still unknown whether these neuron-like cells possess physiological properties of functional neurons and whether they can contribute to the recovery of neuron dysfunction. To answer these questions, we investigated their characteristics by detecting neuronal function-related neurotransmitters and calcium image. The results showed that these cells exhibited functional cholinergic neurons in vitro. Transplantation of these cholinergic neuron-like cells promoted the recovery of spinal cord-injured mice, and they were more effective than BMSCs. The number of cholinergic neurons was increased after injection with BMSC-derived cholinergic neuron-like cells, indicating their high differentiation rate in vivo. Moreover, the proportion of cholinergic neurons in host cells and secretion of acetylcholine were increased, and preservation of neurofilament was also observed in the lesion of mice implanted with BMSC-derived neurons, suggesting the neuronal protection of BMSC-derived neurons. Our findings provide both a simple method to induce the differentiation of BMSCs into cholinergic neuron-like cells and a putative strategy for the therapy of spinal cord injuries.