Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial

Jaillard, Assia; Hommel, Marc; Moisan, Anaïck; Zeffiro, Thomas A.; Favre-Wiki, Isabelle M; Barbieux-Guillot, Marianne; Vadot, Wilfried; Marcel, Sébastien; Lamalle, Laurent; Grand, Sylvie; Detante, Olivier

doi:10.1007/s12975-020-00787-z

Cited by 106 publications

(90 citation statements)

References 54 publications

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“…IV or IA transplantation accounts for the majority of trials, while IT transplantation has also been reported. The results of these studies are mostly similar to the favorable results reported in the acute phase of trials using small samples, while larger randomized trials showed heterogeneous efficacy [ 8 , 11 , 14 , 17 , 22 , 24 , 27 , 28 ]. A large trial performed by Prasad et al included 118 patients, half of which received approximately 3 × 10 7 autologous BMMNCs between 7 and 10 d following the insult [ 14 ].…”

Section: Key Aspects Of Clinical Trialssupporting

confidence: 79%

“…Cell transplantation after a week for up to 6 months is considered to be sub-acute treatment [ 2 , 3 , 5 , 8 , 11 , 13 , 14 , 15 , 17 , 20 , 22 , 24 , 26 , 27 , 28 , 34 , 36 , 42 ]. In addition to BMMNCs, autologous BMSCs are used for ex-vivo expansion within a time frame of approximately 1 month.…”

Section: Key Aspects Of Clinical Trialsmentioning

confidence: 99%

“…This phase II multicenter, parallel-group, randomized accessor blinded trial revealed that, although IV infusion of BMMNCs was safe, it did not exert any beneficial effects (BI) on stroke outcome. Lee et al reported that IV injection of 1 × 10 8 BMSCs resulted in better recovery and reduced mortality for up to 5 years from treatment initiation, compared with randomized controls [ 28 ], whereas Jaillard et al did not report an overall benefit [ 27 ]. Differences in cell processing procedures, patient types, and timing make arriving at a specific conclusion much more difficult.…”

Section: Key Aspects Of Clinical Trialsmentioning

confidence: 99%

“…Lately, stem cell therapy has been recognized as a promising strategy that functionally enhances recovery from ischemic stroke. Thus, a variety of cells, including bone marrow mononuclear cells (BMMNCs) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], bone marrow/adipose-derived stem/stromal cells (BMSCs/ADMSCs) [ 4 , 6 , 7 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], umbilical cord blood cells (UCBCs) and hematopoietic stem cells [ 32 , 33 , 34 , 35 , 36 , 37 ], neural stem cells (NSCs) [ 34 , 36 , 38 , 39 , 40 , 41 , 42 , 43 ], olfactory ensheathing cells (OECs) [ 38 ], and fetal porcine cells [ 44 ], have been explored as candidate donors. Animal studies have indicated that such cells may ameliorate the neurological deficits that follow cerebral stroke, and some have been tested in clinical trials with somewhat favorable results.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Kawabori

Shichinohe

Kuroda

et al. 2020

IJMS

106

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Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.

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Section: Key Aspects Of Clinical Trialssupporting

confidence: 79%

Section: Key Aspects Of Clinical Trialsmentioning

confidence: 99%

Section: Key Aspects Of Clinical Trialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Kawabori

Shichinohe

Kuroda

et al. 2020

IJMS

106

View full text Add to dashboard Cite

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“…An alternative source of cell therapy involves the use of adult progenitor cells derived from bone marrow, including mesenchymal stem cells or their faction -the bone marrow mononuclear cells [22][23][24][25]82]. Both mesenchymal and mononuclear bone marrow cells (BMMCs) are highly anti-inflammatory and neuroprotective in experimental models of stroke [22-25, 82, 83].…”

Section: Stem Cell Therapy For Strokementioning

confidence: 99%

Microglial Plasticity Contributes to Recovery of Bone Marrow Mononuclear Cells during Experimental Stroke

Franco¹,

Cardoso²,

Souza³

et al. 2021

Macrophages

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Brain stroke is an acute neural disorder characterized by obstruction (ischemic) or rupture (hemorrhagic) of blood vessels causing neural damage and subsequent functional impairment. Its pathophysiology is complex and involves a multitude of pathological events including energetic collapse, excitotoxicity, oxidative stress, metabolic acidosis, cell death and neuroinflammation. Despite its clinical importance, there is no effective pharmacological therapies available to diminish secondary damage avowing functional deficits. Considering the failure of pharmacological approaches for stroke, cell therapy came as promising alternative. Different cell types have been investigated in different experimental models with promising results. An important issue regarding the transplantation of stem cells into the damaged CNS tissue is how the pathological environment influences the transplanted cells. It has been established that an exacerbated inflammation in the pathological environment is detrimental to the survival of the transplanted stem cells. This prompted us to develop an experimental strategy to improve the therapeutic actions of bone marrow mononuclear cells (BMMCs) transplanted into the acute phase of brain stroke by modulating microglial activation with minocycline. In this chapter, we first review the basic pathophysiology of ischemic stroke with emphasis on the role of microglia to the pathological outcome. We then review the experimental approach of modulating microglia activation in order to enhance therapeutic actions of BMMCS for experimental stroke. We suggest that such an approach may be applied as an adjuvant therapy to control excessive neuroinflammation in the pathological environment allowing acute transplants and improving therapeutic actions of different kind of stem cells.

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Allogeneic Stem Cell Therapy for Acute Ischemic Stroke

Houkin,

Osanai,

Uchiyama

et al. 2024

JAMA Neurol

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ImportanceCell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow–derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke.ObjectiveTo assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.Design, Setting, and ParticipantsThe Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022.ExposurePatients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset.Main Outcomes and MeasuresThe primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test.ResultsThis study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, −7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups.Conclusions and RelevanceIn this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study.Trial RegistrationClinicalTrials.gov Identifier: NCT02961504

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Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial

Cited by 106 publications

References 54 publications

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Microglial Plasticity Contributes to Recovery of Bone Marrow Mononuclear Cells during Experimental Stroke

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke

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