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Background:

Vascular dementia (VD) is a series of clinical and neurophysiological manifestations caused by cerebrovascular disease. As the human lifespan increases, the number of people affected by age-related dementia is growing at an alarming pace, but no proved therapeutic methods can stop it from getting worse.

Objective:

To investigate the neurorestorative effects of injecting olfactory ensheathing cells (OECs), Schwann cells (SCs), and olfactory receptor neurons (ORNs) into olfactory sub-mucosa in VD patients.

Methods:

A pilot study of double-blind randomized controlled cell therapies was conducted in VD patients (n = 5). Cells were injected into the patients’ olfactory sub-mucosa. Two patients received OEC treatment, one received SC treatment, one ORN treatment, and one OEC combined with ORN. Mental state and cognitive function were observed before treatment and 1, 3, 6, and 12 months after treatment. magnetic resonance imaging (MRI) or computed tomography (CT) was performed before treatment and 12 months after treatment.

Results:

The directional function score on the Mini-Mental Status Examination (MMSE) in the patient who received SC treatment had increased slightly 1 and 3 months after treatment. The scores for orientation, attention, delayed verbal recall, and repetition increased in the ORN group patient 1 month after treatment. The orientation and repetition scores of the ORN group patient continued to increase 3 months after treatment. The scores for attention, delayed verbal recall, and phase 3 command decreased in the OEC and the OEC + ORN group patients after treatment assessment Scores on the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating (CDR) scale also improved in the ORN group patient. Clinical and MRI or CT examinations did not find any side effects from the cell therapy or transplanting procedure.

Conclusion:

All of the cell transplantations were found to be safe. ORN was shown to be a promising therapy for VD patients. Phase II clinical trials of ORN, SC, and OEC therapy are required to verify their effects on VD symptoms, especially ORNs.


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A pilot study of clinical cell therapy for patients with vascular dementia

Show Author's information Yunliang Wang1Xiaoling Guo2Yanqiu Liu1Yan Li2Ying Liu3Di Chen4Juan Xiao4Wenyong Gao4Yajun Liu1Bo Zhou2Ran Liu1Fei Liu5Weidong Chen6Deqiang Guo5Gensheng Mao3Hongyun Huang4( )
Neurological Center, The 960th Hospital of Chinese PLA, Zibo 255300, Shandong, China
Neurological Department, The 981st Hospital of Chinese PLA, Chengde 067000, Hebei, China
Institute of Neurorestoratology, The Third Medical Center of the General Hospital of The PLA, Beijing 100039, China
Beijing Hongtianji Neuroscience Academy, Beijing 100143, China
E.N.T. Department, The 960th Hospital of Chinese PLA, Zibo 255300, Shandong, China
E.N.T. Department, The 981st Hospital of Chinese PLA, Chengde 067000, Hebei, China

Abstract

Background:

Vascular dementia (VD) is a series of clinical and neurophysiological manifestations caused by cerebrovascular disease. As the human lifespan increases, the number of people affected by age-related dementia is growing at an alarming pace, but no proved therapeutic methods can stop it from getting worse.

Objective:

To investigate the neurorestorative effects of injecting olfactory ensheathing cells (OECs), Schwann cells (SCs), and olfactory receptor neurons (ORNs) into olfactory sub-mucosa in VD patients.

Methods:

A pilot study of double-blind randomized controlled cell therapies was conducted in VD patients (n = 5). Cells were injected into the patients’ olfactory sub-mucosa. Two patients received OEC treatment, one received SC treatment, one ORN treatment, and one OEC combined with ORN. Mental state and cognitive function were observed before treatment and 1, 3, 6, and 12 months after treatment. magnetic resonance imaging (MRI) or computed tomography (CT) was performed before treatment and 12 months after treatment.

Results:

The directional function score on the Mini-Mental Status Examination (MMSE) in the patient who received SC treatment had increased slightly 1 and 3 months after treatment. The scores for orientation, attention, delayed verbal recall, and repetition increased in the ORN group patient 1 month after treatment. The orientation and repetition scores of the ORN group patient continued to increase 3 months after treatment. The scores for attention, delayed verbal recall, and phase 3 command decreased in the OEC and the OEC + ORN group patients after treatment assessment Scores on the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating (CDR) scale also improved in the ORN group patient. Clinical and MRI or CT examinations did not find any side effects from the cell therapy or transplanting procedure.

Conclusion:

All of the cell transplantations were found to be safe. ORN was shown to be a promising therapy for VD patients. Phase II clinical trials of ORN, SC, and OEC therapy are required to verify their effects on VD symptoms, especially ORNs.

Keywords: cell therapy, vascular dementia, cognitive evaluation;neurorestorative effects

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Publication history
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Publication history

Received: 08 May 2021
Revised: 05 June 2021
Accepted: 19 June 2021
Published: 05 June 2021
Issue date: June 2021

Copyright

© The authors 2021

Acknowledgements

Huang HY who wrote the first draft of the manuscript was involved in study design, data interpretation, and enrollment of patients. Wang YL and Guo XL involved in study design, recruited patients and involved in data interpretation, reviewing the manuscript, editing, helping with revisions. Liu Y, Gao WY, Xiao J, Liu R, Zhou B and Mao GS were involved in cell culture preparing and quality control. Guo DQ, Chen WD, and Liu F did the injecting procedure. Liu YQ, Li Y, Chen D and Liu YJ were involved in assessment, data collection and analysis.

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