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

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 phosphatidy...

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Main Authors: Chunhui Sun, Jing Shao, Le Su, Jing Zhao, Jianzhong Bi, Shaonan Yang, Shangli Zhang, Jiangang Gao, Junying Miao
Format: Article
Language:English
Published: SAGE Publishing 2013-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368912X657413
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author Chunhui Sun
Jing Shao
Le Su
Jing Zhao
Jianzhong Bi
Shaonan Yang
Shangli Zhang
Jiangang Gao
Junying Miao
author_facet Chunhui Sun
Jing Shao
Le Su
Jing Zhao
Jianzhong Bi
Shaonan Yang
Shangli Zhang
Jiangang Gao
Junying Miao
author_sort Chunhui Sun
collection DOAJ
description 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.
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spelling doaj.art-6941615909344d90b36b9c379a6e9c852022-12-21T20:33:30ZengSAGE PublishingCell Transplantation0963-68971555-38922013-06-012210.3727/096368912X657413Cholinergic Neuron-Like Cells Derived from Bone Marrow Stromal Cells Induced by Tricyclodecane-9-yl-Xanthogenate Promote Functional Recovery and Neural Protection after Spinal Cord InjuryChunhui Sun0Jing Shao1Le Su2Jing Zhao3Jianzhong Bi4Shaonan Yang5Shangli Zhang6Jiangang Gao7Junying Miao8Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, ChinaKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, ChinaKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, ChinaDepartment of Neural Medicine, The Second Hospital of Shandong University, Jinan, ChinaDepartment of Neural Medicine, The Second Hospital of Shandong University, Jinan, ChinaKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, ChinaShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, ChinaKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, ChinaThe 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.https://doi.org/10.3727/096368912X657413
spellingShingle Chunhui Sun
Jing Shao
Le Su
Jing Zhao
Jianzhong Bi
Shaonan Yang
Shangli Zhang
Jiangang Gao
Junying Miao
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
Cell Transplantation
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://doi.org/10.3727/096368912X657413
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