Safety and Clinical Efficacy of Mesenchymal Stem Cell Treatment in Traumatic Spinal Cord Injury, Multiple Sclerosis and Ischemic Stroke - A Systematic Review and Meta-Analysis.
ischemic stroke
mesenchymal stem cells
multiple sclerosis
regenerative medicine
traumatic spinal cord injuries
Journal
Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899
Informations de publication
Date de publication:
2022
2022
Historique:
received:
07
03
2022
accepted:
22
04
2022
entrez:
17
6
2022
pubmed:
18
6
2022
medline:
18
6
2022
Statut:
epublish
Résumé
Mesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential in different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety and clinical effect of MSC treatment in traumatic spinal cord injury (TSCI), multiple sclerosis (MS) and ischemic stroke (IS). A systematic search was performed 2021-12-10 in MEDLINE, EMBASE, Web of Science and Cochrane where clinical studies assessing MSC treatment in TSCI, MS or IS were included. Studies without control group were excluded for efficacy analysis, but included in the safety analysis. For efficacy, AIS score, EDSS score and mRS were used as clinical endpoints and assessed in a meta-analysis using the random effects model. Of 5,548 identified records, 54 studies were included. Twenty-six studies assessed MSC treatment in TSCI, 14 in MS and nine in IS, of which seven, seven and five studies were controlled, respectively. There were seven serious adverse events (SAEs), of which four were related to the surgical procedure and included one death due to complications following the implantation of MSCs. Three SAEs were considered directly related to the MSC treatment and all these had a transient course. In TSCI, a meta-analysis showed no difference in conversion from AIS A to C and a trend toward more patients treated with MSCs improving from AIS A to B as compared to controls ( MSC-treatment is safe in patients with TSCI, MS and IS, although surgical implantation of MSC led to one fatal outcome in TSCI. There was no clear clinical benefit of MSC treatment, but this is not necessarily a proof of inefficacy due to the low number of controlled studies. Future studies assessing efficacy of MSC treatment should aim to do this in randomized, controlled studies.
Sections du résumé
Background
UNASSIGNED
Mesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential in different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety and clinical effect of MSC treatment in traumatic spinal cord injury (TSCI), multiple sclerosis (MS) and ischemic stroke (IS).
Methods
UNASSIGNED
A systematic search was performed 2021-12-10 in MEDLINE, EMBASE, Web of Science and Cochrane where clinical studies assessing MSC treatment in TSCI, MS or IS were included. Studies without control group were excluded for efficacy analysis, but included in the safety analysis. For efficacy, AIS score, EDSS score and mRS were used as clinical endpoints and assessed in a meta-analysis using the random effects model.
Findings
UNASSIGNED
Of 5,548 identified records, 54 studies were included. Twenty-six studies assessed MSC treatment in TSCI, 14 in MS and nine in IS, of which seven, seven and five studies were controlled, respectively. There were seven serious adverse events (SAEs), of which four were related to the surgical procedure and included one death due to complications following the implantation of MSCs. Three SAEs were considered directly related to the MSC treatment and all these had a transient course. In TSCI, a meta-analysis showed no difference in conversion from AIS A to C and a trend toward more patients treated with MSCs improving from AIS A to B as compared to controls (
Interpretation
UNASSIGNED
MSC-treatment is safe in patients with TSCI, MS and IS, although surgical implantation of MSC led to one fatal outcome in TSCI. There was no clear clinical benefit of MSC treatment, but this is not necessarily a proof of inefficacy due to the low number of controlled studies. Future studies assessing efficacy of MSC treatment should aim to do this in randomized, controlled studies.
Identifiants
pubmed: 35711260
doi: 10.3389/fneur.2022.891514
pmc: PMC9196044
doi:
Types de publication
Systematic Review
Langues
eng
Pagination
891514Informations de copyright
Copyright © 2022 Kvistad, Kråkenes, Gjerde, Mustafa, Rekand and Bø.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Lancet Neurol. 2021 Nov;20(11):917-929
pubmed: 34687636
Cell Transplant. 2014;23 Suppl 1:S113-22
pubmed: 25385295
Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(2 Pt 2):72-6
pubmed: 21919233
Brain. 2011 Jun;134(Pt 6):1790-807
pubmed: 21493695
Cytotherapy. 2016 Dec;18(12):1476-1482
pubmed: 27727015
Neurosurgery. 2016 Mar;78(3):436-47; discussion 447
pubmed: 26891377
PLoS One. 2014 Dec 01;9(12):e113936
pubmed: 25436769
Stem Cells Int. 2019 Dec 23;2019:8536785
pubmed: 31949442
Cytotherapy. 2021 Feb;23(2):146-156
pubmed: 32981857
PLoS One. 2015 Aug 04;10(8):e0134920
pubmed: 26241653
Am J Transl Res. 2018 Jan 15;10(1):212-223
pubmed: 29423006
Adv Biomed Res. 2016 Mar 16;5:51
pubmed: 27110548
Cells. 2019 Jul 28;8(8):
pubmed: 31357692
Neural Regen Res. 2020 Sep;15(9):1686-1700
pubmed: 32209773
Lancet Neurol. 2012 Feb;11(2):150-6
pubmed: 22236384
Ann Neurol. 2005 Jun;57(6):874-82
pubmed: 15929052
Trends Pharmacol Sci. 2020 Sep;41(9):653-664
pubmed: 32709406
J Transl Med. 2014 Sep 12;12:253
pubmed: 25209445
Front Cell Neurosci. 2015 Jul 13;9:249
pubmed: 26217178
Neurology. 2021 Feb 16;96(7):e1012-e1023
pubmed: 33472925
Front Immunol. 2021 Aug 26;12:711362
pubmed: 34512632
Stem Cell Res Ther. 2021 Aug 9;12(1):445
pubmed: 34372939
Cell Transplant. 2017 May 9;26(5):891-900
pubmed: 28185615
Transl Stroke Res. 2020 Oct;11(5):910-923
pubmed: 32462427
Br J Neurosurg. 2011 Aug;25(4):516-22
pubmed: 21749185
Lancet Neurol. 2017 May;16(5):360-368
pubmed: 28320635
Stroke. 2016 Jul;47(7):1817-24
pubmed: 27256670
Immunol Invest. 2019 Feb;48(2):160-168
pubmed: 30156938
PLoS One. 2018 May 16;13(5):e0195891
pubmed: 29768414
J Transl Med. 2013 Dec 20;11:315
pubmed: 24355001
Cytotherapy. 2021 Jan;23(1):57-64
pubmed: 33218835
Cytotherapy. 2009;11(7):897-911
pubmed: 19903102
J Transl Med. 2018 Mar 9;16(1):57
pubmed: 29523171
Cytotherapy. 2017 Oct;19(10):1189-1196
pubmed: 28760352
Cytotherapy. 2018 Jun;20(6):806-819
pubmed: 29853256
Mult Scler Relat Disord. 2014 Nov;3(6):696-704
pubmed: 25891548
Cytotherapy. 2013 Jul;15(7):782-91
pubmed: 23731761
Cytotherapy. 2021 Sep;23(9):833-840
pubmed: 33992536
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
J Clin Med. 2019 Dec 02;8(12):
pubmed: 31810187
Cytotherapy. 2016 Aug;18(8):1025-1036
pubmed: 27311799
Stroke. 2019 Oct;50(10):2835-2841
pubmed: 31495331
Cytotherapy. 2018 Jun;20(6):796-805
pubmed: 29784434
Iran J Immunol. 2007 Mar;4(1):50-7
pubmed: 17652844
Sci Adv. 2020 Jul 22;6(30):eaba6884
pubmed: 32832666
Spinal Cord. 2016 Feb;54(2):102-9
pubmed: 26526896
NPJ Regen Med. 2019 Dec 2;4:22
pubmed: 31815001
Curr Stem Cell Res Ther. 2012 Nov;7(6):407-14
pubmed: 23061813
EBioMedicine. 2018 Mar;29:23-30
pubmed: 29449193
Sci Rep. 2021 Nov 9;11(1):21907
pubmed: 34754046
Cell Death Discov. 2018 Aug 20;4:28
pubmed: 30131877
Mult Scler. 2010 Apr;16(4):503-10
pubmed: 20086020
Clin Neurol Neurosurg. 2012 Sep;114(7):935-9
pubmed: 22464434
Brain. 2020 Dec 1;143(12):3574-3588
pubmed: 33253391
Mult Scler. 2018 Apr;24(4):501-511
pubmed: 28381130
Spinal Cord. 2022 Jan;60(1):63-70
pubmed: 34504283
Stem Cell Res Ther. 2014 Nov 17;5(6):126
pubmed: 25406723
Front Cell Dev Biol. 2020 Dec 07;8:603292
pubmed: 33365311
J Neuroimmunol. 2010 Oct 8;227(1-2):185-9
pubmed: 20728948
Stem Cell Res Ther. 2021 Oct 18;12(1):545
pubmed: 34663461
Cytotherapy. 2016 Apr;18(4):518-22
pubmed: 26971680
Cell Transplant. 2014;23 Suppl 1:S65-72
pubmed: 25333752
Front Immunol. 2012 Sep 26;3:297
pubmed: 23056000
Stem Cell Res Ther. 2018 Aug 9;9(1):213
pubmed: 30092840
Cytotherapy. 2017 Mar;19(3):349-359
pubmed: 28089079
CNS Neurosci Ther. 2017 Nov;23(11):866-874
pubmed: 28961381