PMID- 33218835
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20210727
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 23
IP  - 1
DP  - 2021 Jan
TI  - Repeated subarachnoid administrations of allogeneic human umbilical cord 
      mesenchymal stem cells for spinal cord injury: a phase 1/2 pilot study.
PG  - 57-64
LID - S1465-3249(20)30903-8 [pii]
LID - 10.1016/j.jcyt.2020.09.012 [doi]
AB  - BACKGROUND AIMS: Stem cell transplantation is a potential treatment for 
      intractable spinal cord injury (SCI), and allogeneic human umbilical cord 
      mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the 
      advantages of immune privilege, paracrine effect, immunomodulatory function, 
      convenient collection procedure and little ethical concern, and there is an 
      urgent need to develop a safe and effective protocol regarding their clinical 
      application. METHODS: A prospective, single-center, single-arm study in which 
      subjects received four subarachnoid transplantations of hUC-MSCs (1 x 10(6) 
      cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months 
      after final administration) was conducted. At each scheduled time point, safety 
      and efficacy indicators were collected and analyzed accordingly. Adverse events 
      (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) 
      and SCI Functional Rating Scale of the International Association of 
      Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were 
      determined as primary efficacy outcomes, whereas these two indicators at the 
      remaining time points as well as scores of pinprick, light touch, motor and 
      sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel 
      functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were 
      secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was 
      also performed. RESULTS: Safety and efficacy assessments were performed on 102 
      and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), 
      transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed 
      following hUC-MSC transplantation and resolved thoroughly after conservative 
      treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed 
      statistical increases when compared with the baselines at different time points 
      during the study, mainly reflected in the improvement of pinprick, light touch, 
      motor and sphincter scores. Moreover, subjects showed a continuous and remarkable 
      decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder 
      and bowel functions, RUV and MRI, data/imaging at final follow-up showed 
      significant improvements compared with those at first collection. Subgroup 
      analysis found that hUC-MSC transplantation improved neurological functions 
      regardless of injury characteristics, including level, severity and chronicity. 
      CONCLUSIONS: The authors' present protocol demonstrates that intrathecal 
      administration of' allogeneic hUC-MSCs at a dose of 10(6) cells/kg once a month 
      for 4 months is safe and effective and leads to significant improvement in 
      neurological dysfunction and recovery of quality of life.
CI  - Copyright (c) 2020 International Society for Cell & Gene Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Pang, Mao
AU  - Pang M
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Du, Cong
AU  - Du C
AD  - Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
FAU - Liu, Zhong-Yu
AU  - Liu ZY
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Chen, Zi-Hao
AU  - Chen ZH
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Wang, Nan-Xiang
AU  - Wang NX
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Zhang, Liang-Ming
AU  - Zhang LM
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Chen, Yu-Yong
AU  - Chen YY
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Mo, Jian
AU  - Mo J
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Dong, Jian-Wen
AU  - Dong JW
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Xie, Pei-Gen
AU  - Xie PG
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Wang, Qi-You
AU  - Wang QY
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China.
FAU - Liu, Bin
AU  - Liu B
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China. Electronic address: liubin6@mail.sysu.edu.cn.
FAU - Rong, Li-Min
AU  - Rong LM
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University, Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery, Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, People's Republic of 
      China. Electronic address: ronglm@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201118
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Immunologic Factors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Humans
MH  - Immunologic Factors/therapeutic use
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/methods
MH  - *Mesenchymal Stem Cells
MH  - Middle Aged
MH  - Pilot Projects
MH  - Prospective Studies
MH  - Quality of Life
MH  - Spinal Cord Injuries/*therapy
MH  - Subarachnoid Space/physiopathology
MH  - Umbilical Cord/*cytology
MH  - Young Adult
OTO - NOTNLM
OT  - clinical trial
OT  - efficacy
OT  - human umbilical cord mesenchymal stem cell
OT  - safety
OT  - spinal cord injury
OT  - subarachnoid transplantation
EDAT- 2020/11/22 06:00
MHDA- 2021/07/28 06:00
CRDT- 2020/11/21 05:29
PHST- 2020/05/21 00:00 [received]
PHST- 2020/08/12 00:00 [revised]
PHST- 2020/09/30 00:00 [accepted]
PHST- 2020/11/22 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2020/11/21 05:29 [entrez]
AID - S1465-3249(20)30903-8 [pii]
AID - 10.1016/j.jcyt.2020.09.012 [doi]
PST - ppublish
SO  - Cytotherapy. 2021 Jan;23(1):57-64. doi: 10.1016/j.jcyt.2020.09.012. Epub 2020 Nov 
      18.