PMID- 36759901
OWN - NLM
STAT- MEDLINE
DCOM- 20230213
LR  - 20230217
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Feb 9
TI  - Safety and efficacy outcomes after intranasal administration of neural stem cells 
      in cerebral palsy: a randomized phase 1/2 controlled trial.
PG  - 23
LID - 10.1186/s13287-022-03234-y [doi]
LID - 23
AB  - BACKGROUND: Neural stem cells (NSCs) are believed to have the most therapeutic 
      potential for neurological disorders because they can differentiate into various 
      neurons and glial cells. This research evaluated the safety and efficacy of 
      intranasal administration of NSCs in children with cerebral palsy (CP). The 
      functional brain network (FBN) analysis based on electroencephalogram (EEG) and 
      voxel-based morphometry (VBM) analysis based on T1-weighted images were performed 
      to evaluate functional and structural changes in the brain. METHODS: A total of 
      25 CP patients aged 3-12 years were randomly assigned to the treatment group 
      (n = 15), which received an intranasal infusion of NSCs loaded with nasal patches 
      and rehabilitation therapy, or the control group (n = 10) received rehabilitation 
      therapy only. The primary endpoints were the safety (assessed by the incidence of 
      adverse events (AEs), laboratory and imaging examinations) and the changes in the 
      Gross Motor Function Measure-88 (GMFM-88), the Activities of Daily Living (ADL) 
      scale, the Sleep Disturbance Scale for Children (SDSC), and some adapted scales. 
      The secondary endpoints were the FBN and VBM analysis. RESULTS: There were only 
      four AEs happened during the 24-month follow-up period. There was no significant 
      difference in the laboratory examinations before and after treatment, and the 
      magnetic resonance imaging showed no abnormal nasal and intracranial masses. 
      Compared to the control group, patients in the treatment group showed apparent 
      improvements in GMFM-88 and ADL 24 months after treatment. Compared with the 
      baseline, the scale scores of the Fine Motor Function, Sociability, Life 
      Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the 
      treatment group 24 months after treatment, while the SDSC score decreased 
      considerably. Compared with baseline, the FBN analysis showed a substantial 
      decrease in brain network energy, and the VBM analysis showed a significant 
      increase in gray matter volume in the treatment group after NSCs treatment. 
      CONCLUSIONS: Our results showed that intranasal administration of NSCs was 
      well-tolerated and potentially beneficial in children with CP. TRIAL 
      REGISTRATION: The study was registered in ClinicalTrials.gov (NCT03005249, 
      registered 29 December 2016, https://www. CLINICALTRIALS: 
      gov/ct2/show/NCT03005249 ) and the Medical Research Registration Information 
      System (CMR-20161129-1003).
CI  - (c) 2023. The Author(s).
FAU - Lv, Zhongyue
AU  - Lv Z
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Li, Ying
AU  - Li Y
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Wang, Yachen
AU  - Wang Y
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Cong, Fengyu
AU  - Cong F
AD  - School of Biomedical Engineering, Faculty of Electronic Information and 
      Electrical Engineering, Dalian University of Technology, Dalian, Liaoning 
      Province, China.
AD  - Faculty of Information Technology, University of Jyvaskyla, 40014, Jyvaskyla, 
      Finland.
FAU - Li, Xiaoyan
AU  - Li X
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Cui, Wanming
AU  - Cui W
AD  - Department of Ent, The First Affiliated Hospital of Dalian Medical University, 
      Dalian, Liaoning, China.
FAU - Han, Chao
AU  - Han C
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Wei, Yushan
AU  - Wei Y
AD  - Scientific Research Department, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning, China.
FAU - Hong, Xiaojun
AU  - Hong X
AD  - Neurophysiological Center, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning, China.
FAU - Liu, Yong
AU  - Liu Y
AD  - Department of Rehabilitation, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning, China.
FAU - Ma, Luyi
AU  - Ma L
AD  - Department of Pediatrics, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning, China.
FAU - Jiao, Yang
AU  - Jiao Y
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
AD  - Department of Neurology, The First Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning, China.
FAU - Zhang, Chi
AU  - Zhang C
AD  - School of Biomedical Engineering, Faculty of Electronic Information and 
      Electrical Engineering, Dalian University of Technology, Dalian, Liaoning 
      Province, China.
FAU - Li, Huanjie
AU  - Li H
AD  - School of Biomedical Engineering, Dalian University of Technology, Dalian, 
      Liaoning, China.
FAU - Jin, Mingyan
AU  - Jin M
AD  - School of Biomedical Engineering, Faculty of Electronic Information and 
      Electrical Engineering, Dalian University of Technology, Dalian, Liaoning 
      Province, China.
FAU - Wang, Liang
AU  - Wang L
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Ni, Shiwei
AU  - Ni S
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China.
FAU - Liu, Jing
AU  - Liu J
AUID- ORCID: 0000-0002-0493-296X
AD  - Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian 
      Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, 
      Liaoning, China. liujing@dmu.edu.cn.
AD  - Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 
      Liaoning, China. liujing@dmu.edu.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT03005249
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230209
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
SB  - IM
MH  - Child
MH  - Humans
MH  - *Cerebral Palsy/therapy
MH  - Activities of Daily Living
MH  - Administration, Intranasal
MH  - Brain/diagnostic imaging
MH  - *Neural Stem Cells
PMC - PMC9910250
OTO - NOTNLM
OT  - Cerebral palsy
OT  - Clinical trials
OT  - Electroencephalogram
OT  - Functional brain network
OT  - Intranasal administration
OT  - Neural stem cells
COIS- The authors declare that they have no competing interests.
EDAT- 2023/02/11 06:00
MHDA- 2023/02/14 06:00
PMCR- 2023/02/09
CRDT- 2023/02/10 00:07
PHST- 2022/04/27 00:00 [received]
PHST- 2022/06/05 00:00 [accepted]
PHST- 2023/02/10 00:07 [entrez]
PHST- 2023/02/11 06:00 [pubmed]
PHST- 2023/02/14 06:00 [medline]
PHST- 2023/02/09 00:00 [pmc-release]
AID - 10.1186/s13287-022-03234-y [pii]
AID - 3234 [pii]
AID - 10.1186/s13287-022-03234-y [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2023 Feb 9;14(1):23. doi: 10.1186/s13287-022-03234-y.