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Journal of Neurorestoratology  2021, Vol. 9 Issue (2): 137-150    doi: 10.26599/JNR.2021.9040011
Research Article     
A pilot study of clinical cell therapy for patients with vascular dementia
Yunliang Wang1,Xiaoling Guo2,Yanqiu Liu1,Yan Li2,Ying Liu3,Di Chen4,Juan Xiao4,Wenyong Gao4,Yajun Liu1,Bo Zhou2,Ran Liu1,Fei Liu5,Weidong Chen6,Deqiang Guo5,Gensheng Mao3,Hongyun Huang4,(✉)()
1Neurological Center, The 960th Hospital of Chinese PLA, Zibo 255300, Shandong, China
2Neurological Department, The 981st Hospital of Chinese PLA, Chengde 067000, Hebei, China
3Institute of Neurorestoratology, The Third Medical Center of the General Hospital of The PLA, Beijing 100039, China
4Beijing Hongtianji Neuroscience Academy, Beijing 100143, China
5E.N.T. Department, The 960th Hospital of Chinese PLA, Zibo 255300, Shandong, China
6E.N.T. Department, The 981st Hospital of Chinese PLA, Chengde 067000, Hebei, China
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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.



Key wordsvascular dementia      cell therapy      cognitive evaluation;neurorestorative effects     
Received: 08 May 2021      Published: 19 October 2021
Corresponding Authors: Hongyun Huang     E-mail: huanghongyun001@126.com
Cite this article:

Yunliang Wang,Xiaoling Guo,Yanqiu Liu,Yan Li,Ying Liu,Di Chen,Juan Xiao,Wenyong Gao,Yajun Liu,Bo Zhou,Ran Liu,Fei Liu,Weidong Chen,Deqiang Guo,Gensheng Mao,Hongyun Huang. A pilot study of clinical cell therapy for patients with vascular dementia. Journal of Neurorestoratology, 2021, 9: 137-150.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2021.9040011     OR     http://jnr.tsinghuajournals.com/Y2021/V9/I2/137

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Fig. 1Diagram of cell injection and migration. After the cells were injected into the olfactory sub-mucosa, they migrated into the olfactory bulb and then to the lesion area. Reproduced from Ref. [14] with permission from the authors, ? the authors.
Assessment scoreBaseline1 month after treatment3 months after treatment6 months after treatment1 year after treatment
SC group (n = 1) Total68866
Orientation23333
Immediate recall23333
Attention00000
Delayed verbal recall00000
Naming22200
Repetition00000
3-stage command00000
Writing00000
OEC group (n = 2)Patient ATotal1515121010
Orientation56655
Immediate recall12000
Attention11111
Delayed verbal recall00000
Naming22222
Repetition11111
3-stage command31100
Writing11000
Patient BTotal1718131312
Orientation75444
Immediate recall23222
Attention11111
Delayed verbal recall12000
Naming22222
Repetition01110
3-stage command33222
Writing00000
ORN group (n = 1) Total1523242424
Orientation45666
Immediate recall33333
Attention05555
Delayed verbal recall02111
Naming22222
Repetition00111
3-stage command33333
Writing11111
OEC + ORN group (n = 1) Total2724242323
Orientation99999
Immediate recall33333
Attention53333
Delayed verbal recall22211
Naming22222
Repetition11111
3-stage command32222
Writing11111
Table 1Functional scores on MMSE.
Assessment scoreBaseline1 month after treatment3 months after treatment6 months after treatment1 year after treatment
SC group (n=1) Total00000
Visuospatial/executive00000
Naming00000
Attention00000
Language00000
Abstraction00000
Delayed recall00000
Orientation00000
OEC group (n = 2)Patient ATotal1011766
Visuospatial/executive01211
Naming33333
Attention32000
Language00000
Abstraction22000
Delayed recall00000
Orientation23222
Patient BTotal1311865
Visuospatial/executive00000
Naming33333
Attention12100
Language11000
Abstraction12110
Delayed recall10000
Orientation63322
ORN group (n = 1) Total58101111
Visuospatial/executive12233
Naming23333
Attention00000
Language00000
Abstraction00222
Delayed recall00000
Orientation23333
OEC + ORN group (n = 1) Total2320191919
Visuospatial/executive33333
Naming33333
Attention77666
Language21111
Abstraction20000
Delayed recall00000
Orientation66666
Table 2Functional scores on MoCA.
Assessment scoreBaseline1 month after treatment3 months after treatment6 months after treatment1 year after treatment
SC group (n = 1) CDR33333
Memory32233
Orientation22222
Judgment and problem solving33333
Community affairs33333
Home and hobbies33333
Personal care33333
OEC group (n = 2)Patient ACDR13333
Memory23333
Orientation33333
Judgment and problem solving13333
Community affairs13333
Home and hobbies13333
Personal care03333
Patient BCDR22222
Memory22222
Orientation11111
Judgment and problem solving22333
Community affairs22222
Home and hobbies33333
Personal care22222
ORN group (n = 1) CDR22111
Memory22222
Orientation20.50.50.50.5
Judgment and problem solving21111
Community affairs21111
Home and hobbies22222
Personal care02110
OEC + ORN group (n = 1) CDR11111
Memory11111
Orientation11111
Judgment and problem solving11111
Community affairs0.51111
Home and hobbies11111
Personal care00000
Table 3Functional scores on CDR scale.
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