JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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Olig2⁺ single-colony-derived cranial bone-marrow mesenchymal stem cells achieve improved regeneration in a cuprizone-induced demyelination mouse model

Author(s): Deqing PENG, Ruijie LU, Leyao L�, Qing YAO, Kaichuang YANG, Yunfeng XU, Xiaoming FENG, Ruolang PAN, Yuyuan MA
Affiliation(s): Center for Rehabilitation Medicine, Department of Neurosurgery, Zhejiang Provincial People�s Hospital (Affiliated People�s Hospital, Hangzhou Medical College),Hangzhou310014,China; more
Corresponding email(s): fengxiaoming2022@163.com, yuyuan_ma98246@163.com
Key Words: Cranial bone marrow; Single colony; Mesenchymal stem cells; Oligodendrocytes; Demyelination

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Deqing PENG, Ruijie LU, Leyao L�, Qing YAO, Kaichuang YANG, Yunfeng XU, Xiaoming FENG, Ruolang PAN, Yuyuan MA. Olig2⁺ single-colony-derived cranial bone-marrow mesenchymal stem cells achieve improved regeneration in a cuprizone-induced demyelination mouse model[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300790

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author="Deqing PENG, Ruijie LU, Leyao L�, Qing YAO, Kaichuang YANG, Yunfeng XU, Xiaoming FENG, Ruolang PAN, Yuyuan MA",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300790"
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%T Olig2⁺ single-colony-derived cranial bone-marrow mesenchymal stem cells achieve improved regeneration in a cuprizone-induced demyelination mouse model
%A Deqing PENG
%A Ruijie LU
%A Leyao L�
%A Qing YAO
%A Kaichuang YANG
%A Yunfeng XU
%A Xiaoming FENG
%A Ruolang PAN
%A Yuyuan MA
%J Journal of Zhejiang University SCIENCE B
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doi="https://doi.org/10.1631/jzus.B2300790"

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T1 - Olig2⁺ single-colony-derived cranial bone-marrow mesenchymal stem cells achieve improved regeneration in a cuprizone-induced demyelination mouse model
A1 - Deqing PENG
A1 - Ruijie LU
A1 - Leyao L�
A1 - Qing YAO
A1 - Kaichuang YANG
A1 - Yunfeng XU
A1 - Xiaoming FENG
A1 - Ruolang PAN
A1 - Yuyuan MA
J0 - Journal of Zhejiang University Science B
SP - 1108
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%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2300790"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Oligodendrocytes are the myelinating cells of the central nervous system. Brain injury and neurodegenerative disease often lead to oligodendrocyte death and subsequent demyelination-related pathological changes, resulting in neurological defects and cognitive impairment (Spaas et al., 2021; Zhang J et al., 2022). Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system. The pathology of MS is characterized by the loss of myelin, oligodendrocytes, and axons in the brain, brain stem, and spinal cord, as well as by white matter lesions (Lassmann et al., 2007). Unfortunately, no definitive cure for MS has been developed. Immunomodulatory and anti-inflammatory drugs are effective in the relapsing-remitting phase of MS because they reduce the frequency of relapses and the formation of inflammatory lesions; however, they do not alter the course of progressive MS and are insufficient to cure chronic neurological dysfunction (Xiao et al., 2015; Zhang et al., 2021). The treatment outcome is even worse for MS patients with primary and secondary progressions. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. MSCs are easy to expand in vitro and exhibit low immunogenicity, no tumorigenic risks, and ethical controversies, making them a promising candidate for regenerative medicine (Zhang L et al., 2022; Xu et al., 2023). Many studies have confirmed the neural differentiation potential of MSCs under certain conditions, making them a prime candidate for treating neurodegenerative diseases (Jang et al., 2010; Yan et al., 2013). The present study investigated the effects of cranial bone-marrow mesenchymal stem cells (cBMMSCs) and oligodendrocyte-specific protein 2-positive (Olig2+) single-colony-derived cBMMSC (sc-cBMMSC), isolated in our previous work (Yang et al., 2022), in a central nervous system demyelination mouse model.

Olig2⁺单克隆颅骨间充质干细胞在双环己酮草酰二腙（CPZ）诱导的小鼠脱髓鞘模型中促再生作用研究

彭德清¹，卢睿杰²，吕乐瑶²，姚情³，杨开创¹，徐云峰⁴，冯小明⁴，潘若浪⁵，麻育源¹
¹浙江省人民医院（杭州医学院附属人民医院）康复中心，神经外科，中国杭州市， 310014
²温州医科大学附属第二临床医学院，中国温州市， 325035
³温州医科大学药学院，中国温州市， 325035
⁴嘉兴市第一医院（嘉兴大学附属医院）神经外科，中国嘉兴市， 314001
⁵浙江省细胞药物与应用技术研究重点实验室，中国杭州市， 311122
摘要：多发性硬化症是中枢神经系统的主要脱髓鞘疾病，目前尚无有效治疗方法。本研究探讨了颅骨间充质干细胞（cBMMSC）和Olig2⁺单克隆来源cBMMSC（sc-cBMMSC）在双环己酮草酰二腙（CPZ）诱导的中枢神经系统脱髓鞘小鼠模型中的作用。通过尾静脉输注cBMMSC和Olig2⁺ sc-cBMMSC，剂量为1×10⁶个细胞每100微升磷酸盐缓冲液（PBS），每周一次，给药两周。治疗完成一周后，对每组小鼠进行相关指标评估。结果表明，cBMMSC移植可显著提高CPZ诱导的脱髓鞘小鼠在转棒、悬挂和水迷宫试验中的能力；抑制小鼠外周血和中枢神经系统中TNF-α、IL-1β和IL-6等炎症因子的水平；此外，小鼠病理结构也得到改善，具体表现在髓鞘得到显著恢复，以及Olig2和Syn表达增加。值得注意的是，与cBMMSC相比，Olig2⁺ sc-cBMMSC更为显著地改善了CPZ动物的行为学、髓鞘修复和神经细胞再生。这些发现表明，颅骨髓来源的干细胞在脱髓鞘中具有修复作用，这可能归因于其对少突胶质细胞的免疫调节和保护。Olig2⁺ sc-cBMMSC移植效果更为显著，进一步证实了间充质干细胞的异质性应被考虑和利用以提高对特定疾病的治疗效果。

关键词组：颅骨骨髓；单克隆；间充质干细胞；少突胶质细胞；脱髓鞘

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Olig2+单克隆颅骨间充质干细胞在双环己酮草酰二腙（CPZ）诱导的小鼠脱髓鞘模型中促再生作用研究

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Reference

Olig2⁺单克隆颅骨间充质干细胞在双环己酮草酰二腙（CPZ）诱导的小鼠脱髓鞘模型中促再生作用研究