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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Meta-Analysis

Efficacy and Safety of Bone Marrow Derived Stem Cell Therapy for Ischemic Stroke: Evidence from Network Meta-analysis

Author(s): Xing Wang, Jingguo Yang, Chao You, Xinjie Bao* and Lu Ma*

Volume 19, Issue 8, 2024

Published on: 23 August, 2023

Page: [1102 - 1110] Pages: 9

DOI: 10.2174/1574888X18666230823094531

Price: $65

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Abstract

Background: Several types of stem cells are available for the treatment of stroke patients. However, the optimal type of stem cell remains unclear.

Objective: To analyze the effects of bone marrow-derived stem cell therapy in patients with ischemic stroke by integrating all available direct and indirect evidence in network meta-analyses.

Methods: We searched several databases to identify randomized clinical trials comparing clinical outcomes of bone marrow-derived stem cell therapy vs. conventional treatment in stroke patients. Pooled relative risks (RRs) and mean differences (MDs) were reported. The surface under the cumulative ranking (SUCRA) was used to rank the probabilities of each agent regarding different outcomes.

Results: Overall, 11 trials with 576 patients were eligible for analysis. Three different therapies, including mesenchymal stem cells (MSCs), mononuclear stem cells (MNCs), and multipotent adult progenitor cells (MAPCs), were assessed. The direct analysis demonstrated that stem cell therapy was associated with significantly reduced all-cause mortality rates (RR 0.55, 95% CI 0.33 to 0.93; I2=0%). Network analysis demonstrated MSCs ranked first in reducing mortality (RR 0.42, 95% CrI 0.15 to 0.86) and improving modified Rankin Scale score (MD -0.59 95% CI -1.09 to -0.09), with SUCRA values 80%, and 98%, respectively. Subgroup analysis showed intravenous transplantation was superior to conventional therapy in reducing all-cause mortality (RR 0.53, 95% CrI 0.29 to 0.88).

Conclusion: Using stem cell transplantation was associated with reduced risk of death and improved functional outcomes in patients with ischemic stroke. Additional large trials are warranted to provide more conclusive evidence.

Graphical Abstract

[1]
Strong K, Mathers C, Bonita R. Preventing stroke: Saving lives around the world. Lancet Neurol 2007; 6(2): 182-7.
[http://dx.doi.org/10.1016/S1474-4422(07)70031-5] [PMID: 17239805]
[2]
Feigin VL, Vos T, Alahdab F, et al. Burden of neurological disorders across the US from 1990-2017. JAMA Neurol 2021; 78(2): 165-76.
[http://dx.doi.org/10.1001/jamaneurol.2020.4152] [PMID: 33136137]
[3]
Wright L, Hill KM, Bernhardt J, et al. Stroke management: Updated recommendations for treatment along the care continuum. Intern Med J 2012; 42(5): 562-9.
[http://dx.doi.org/10.1111/j.1445-5994.2012.02774.x] [PMID: 22616960]
[4]
Stinear CM, Lang CE, Zeiler S, Byblow WD. Advances and challenges in stroke rehabilitation. Lancet Neurol 2020; 19(4): 348-60.
[http://dx.doi.org/10.1016/S1474-4422(19)30415-6] [PMID: 32004440]
[5]
Johnston K, Chapman S, Mehndiratta P, Johansen M, Southerland A, McMurry T. Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke. Vasc Health Risk Manag 2014; 10: 75-87.
[http://dx.doi.org/10.2147/VHRM.S39213] [PMID: 24591838]
[6]
Maltman DJ, Hardy SA, Przyborski SA. Role of mesenchymal stem cells in neurogenesis and nervous system repair. Neurochem Int 2011; 59(3): 347-56.
[http://dx.doi.org/10.1016/j.neuint.2011.06.008] [PMID: 21718735]
[7]
Dabrowska S, Andrzejewska A, Lukomska B, Janowski M. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles. J Neuroinflammation 2019; 16(1): 178.
[http://dx.doi.org/10.1186/s12974-019-1571-8] [PMID: 31514749]
[8]
Yang Y, Ye Y, Su X, He J, Bai W, He X. MSCs-derived exosomes and neuroinflammation, neurogenesis and therapy of traumatic brain injury. Front Cell Neurosci 2017; 11: 55.
[http://dx.doi.org/10.3389/fncel.2017.00055] [PMID: 28293177]
[9]
Janowski M, Wagner DC, Boltze J. Stem cell–based tissue replacement after stroke. Stroke 2015; 46(8): 2354-63.
[http://dx.doi.org/10.1161/STROKEAHA.114.007803] [PMID: 26106118]
[10]
Hess DC, Wechsler LR, Clark WM, et al. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2017; 16(5): 360-8.
[http://dx.doi.org/10.1016/S1474-4422(17)30046-7] [PMID: 28320635]
[11]
Prasad K, Sharma A, Garg A, et al. Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: A multicentric, randomized trial. Stroke 2014; 45(12): 3618-24.
[http://dx.doi.org/10.1161/STROKEAHA.114.007028] [PMID: 25378424]
[12]
Prasad K, Kumar A, Rawat D. Stem cell therapy in ischemic stroke: A systematic review and meta-analysis of randomized controlled trials. Ann Indian Acad Neurol 2021; 24(2): 164.
[http://dx.doi.org/10.4103/aian.AIAN_384_20] [PMID: 34220058]
[13]
Boncoraglio GB, Ranieri M, Bersano A, Parati EA, Del Giovane C. Stem cell transplantation for ischemic stroke. Cochrane Libr 2019; 2019(5): CD007231.
[http://dx.doi.org/10.1002/14651858.CD007231.pub3] [PMID: 31055832]
[14]
Law ZK, Tan HJ, Chin SP, et al. The effects of intravenous infusion of autologous mesenchymal stromal cells in patients with subacute middle cerebral artery infarct: A phase 2 randomized controlled trial on safety, tolerability and efficacy. Cytotherapy 2021; 23(9): 833-40.
[http://dx.doi.org/10.1016/j.jcyt.2021.03.005] [PMID: 33992536]
[15]
Chung JW, Chang WH, Bang OY, et al. Efficacy and safety of intravenous mesenchymal stem cells for ischemic stroke. Neurology 2021; 96(7): e1012-23.
[http://dx.doi.org/10.1212/WNL.0000000000011440] [PMID: 33472925]
[16]
Savitz SI, Yavagal D, Rappard G, et al. A phase 2 randomized, sham-controlled trial of internal carotid artery infusion of autologous bone marrow–derived ALD-401 cells in patients with recent stable ischemic stroke (RECOVER-Stroke). Circulation 2019; 139(2): 192-205.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030659] [PMID: 30586746]
[17]
Shichinohe H, Kuroda S, Maruichi K, et al. Bone marrow stromal cells and bone marrow-derived mononuclear cells: Which are suitable as cell source of transplantation for mice infarct brain? Neuropathology 2010; 30(2): 113-22.
[http://dx.doi.org/10.1111/j.1440-1789.2009.01050.x] [PMID: 19737360]
[18]
Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations. Ann Intern Med 2015; 162(11): 777-84.
[http://dx.doi.org/10.7326/M14-2385] [PMID: 26030634]
[19]
JPT Higgins SGE. the Cochrane Handbook for Systematic Reviews of Interventions. Oxford: The Cochrane Collaboration 2011.
[20]
Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336(7650): 924-6.
[http://dx.doi.org/10.1136/bmj.39489.470347.AD] [PMID: 18436948]
[21]
Salanti G, Ades AE, Ioannidis JPA. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: An overview and tutorial. J Clin Epidemiol 2011; 64(2): 163-71.
[http://dx.doi.org/10.1016/j.jclinepi.2010.03.016] [PMID: 20688472]
[22]
Jaillard A, Hommel M, Moisan A, et al. Autologous mesenchymal stem cells improve motor recovery in subacute ischemic stroke: A randomized clinical trial. Transl Stroke Res 2020; 11(5): 910-23.
[http://dx.doi.org/10.1007/s12975-020-00787-z] [PMID: 32462427]
[23]
Bhatia V, Gupta V, Khurana D, Sharma RR, Khandelwal N. Randomized assessment of the safety and efficacy of intra-arterial infusion of autologous stem cells in subacute ischemic stroke. AJNR Am J Neuroradiol 2018; 39(5): 899-904.
[http://dx.doi.org/10.3174/ajnr.A5586] [PMID: 29545253]
[24]
Jin Y, Ying L, Yu G, Nan G. Analysis of the long-term effect of bone marrow mononuclear cell transplantation for the treatment of cerebral infarction. Int J Clin Exp Med 2017; 10: 3059-68.
[25]
Dinghua L, Bojun H, Shanshan H, et al. Transplanting autologous mesenchymal nerve stem cells in the treatment of cerebral infarction. Chinese J Phys Med Rehab 2014; 36(6): 425-8.
[http://dx.doi.org/10.3760/cma.j.issn.0254-1424.2014.06.006]
[26]
Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 2010; 28(6): 1099-106.
[http://dx.doi.org/10.1002/stem.430] [PMID: 20506226]
[27]
Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005; 57(6): 874-82.
[http://dx.doi.org/10.1002/ana.20501] [PMID: 15929052]
[28]
Chumnanvej S, Chumnanvej S. Autologous bone-marrow mononuclear stem cell therapy in patients with stroke: A meta-analysis of comparative studies. Biomed Eng Online 2020; 19(1): 74.
[http://dx.doi.org/10.1186/s12938-020-00819-7] [PMID: 32993677]
[29]
Kawabori M, Shichinohe H, Kuroda S, Houkin K. Clinical trials of stem cell therapy for cerebral ischemic stroke. Int J Mol Sci 2020; 21(19): 7380.
[http://dx.doi.org/10.3390/ijms21197380] [PMID: 33036265]
[30]
Rosado-de-Castro PH, Schmidt FR, Battistella V, et al. Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. Regen Med 2013; 8(2): 145-55.
[http://dx.doi.org/10.2217/rme.13.2] [PMID: 23477395]
[31]
Kawabori M, Kuroda S, Sugiyama T, et al. Intracerebral, but not intravenous, transplantation of bone marrow stromal cells enhances functional recovery in rat cerebral infarct: An optical imaging study. Neuropathology 2012; 32(3): 217-26.
[http://dx.doi.org/10.1111/j.1440-1789.2011.01260.x] [PMID: 22007875]

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