Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

Cohen, Jeffrey A.; Imrey, Peter B.; Planchon, Sarah M.; Bermel, Robert; Fisher, Elizabeth; Fox, Robert J.; Bar‐Or, Amit; Sharp, Susan L; Skaramagas, T. T.; Jagodnik, P.; Karafa, Matt; Morrison, Shannon L.; Koç, Jane Reese; Gerson, Stanton L.; Lazarus, Hillard M.

doi:10.1177/1352458517703802

Cited by 94 publications

(91 citation statements)

References 31 publications

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“…Nevertheless, an interesting finding was that the highest secretion of IL‐6, IL‐8, and VEGF was detected in MSC‐CM of patients with the lowest number of WM lesions at baseline. As MS8 had the lowest number of lesions and his MSCs expressed the highest amount of the top analytes, he was followed by MS4 who had 60 lesions and expressed the 2nd highest amount. While this correlation was not reflected in the efficacy of treatment in this study, it would be valuable to investigate the biological and therapeutic properties of the MS‐MSCs compared to control individuals and the effect of disease severity in terms of loss of white matter on MSCs and CM‐MSCs content.…”

Section: Discussionmentioning

confidence: 99%

“…In previous clinical studies, the optimal route of stem cell injection, frequency, and number of cells injected has varied and is yet to be determined . In a preclinical study, direct intraventricular MSCs injection has been reported to be more effective in the EAE model compared to the intravenous route .…”

Section: Discussionmentioning

confidence: 99%

“…In another in vivo study, MSC‐CM attenuated neural degeneration in a spinocerebellar ataxia mice model . A number of promising clinical trials using different sources, doses, and routes of MSCs injections have been conducted, none of them investigated the clinical implications of injecting MSCs‐CM . Thus examining the clinical reproducibility of the encouraging preclinical evidence of the benefits of MSC‐CM is necessary.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy

et al. 2017

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SummaryAimsThis open‐label prospective phase I/IIa clinical study used autologous bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) followed by mesenchymal stromal cells conditioned media (MSC‐CM) for the first time to treat multiple sclerosis (MS) patients. The primary goal was to assess the safety and feasibility and the secondary was efficacy. The correlation between the MSC‐CM content and treatment outcome was investigated.MethodsTen MS patients who failed conventional therapy were enrolled. Adverse events were recorded to assess safety. The Expanded Disability Status Scale (EDSS) was the primary efficacy measurement, the secondary included clinical (25WFT, 9‐PHT), cognitive (MMS), ophthalmology (OCT, VEP), and radiological (MRI lesion and volume) tests. The MSCs‐CM concentration of 27 inflammatory biomarkers was investigated.ResultsThe treatment protocol was well tolerated by patients. There was an overall trend of improvement in all the tests, except the lesion volume which increased significantly. A decrease of 4 and 3.5 points on the EDSS was achieved in two patients. We report a correlation between a decreased lesion number at baseline and higher IL‐6, IL‐8, and VEGF MSC‐CM content.ConclusionThe used protocol was safe and feasible with possible efficacy. The addition of MSC‐CM could be related to the magnitude of EDSS improvement observed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy

et al. 2017

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“…Among these studies, 3 were excluded due to less than 5 cases, 3 due to lack of full texts, 5 due to being review and conference articles, and 5 due to relevant data not being extractable. Finally, in this meta-analysis, 9 studies [10][11][12][13][14][15][16][17][18] on aMSCs for the treatment of MS were analyzed which included 133 transplanted patients (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis: A Meta-Analysis

Zhou

Zhang

Xue

et al. 2019

Stem Cells International

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Multiple sclerosis (MS) is considered to be a central nervous system (CNS) chronic inflammatory demyelinating disease, affecting more than 2 million individuals worldwide. In this meta-analysis, we aimed to assess the safety and efficacy of autologous mesenchymal stem cells (aMSCs) in treating MS patients. The PubMed, Embase, Cochrane, Web of Science, and Clinical Trial databases were searched in September 2019. The analysis was conducted for three endpoints: transplant-related mortality (TRM), rate of disease progression, and no evidence of disease activity (NEDA) status. RevMan and the metaprop command of the meta package in R was used in assessing the efficacy and safety of aMSCs. Subgroup analyses were performed for exploration of heterogeneity regarding outcomes. Nine studies comprising 133 patients were included in the meta-analysis. The pooled estimate of TRM was 0% (95% confidence interval (CI) 0%–0.3%). The rate of progression was 16% at 6 months (95% CI 10%–27%) and 35% at 1 year (95% CI 27%–46%). Lower 6-month and 1-year progression rates were significantly associated with intrathecal injection (p=0.02; p=0.003). The pooled proportion of NEDA patients at 6 months was 72% (95% CI 58%–89%) and at 1 year was 62% (95% CI 42%–81%). Cell transplantation with aMSCs in MS patients is safe, with the largest benefit profile obtained in patients with aMSCs intrathecal injection.

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“…In 2017, more than ten publications used expanded to treat some diseases in both local injection and infusion in Pubmed [1][2][3][4][5][6][7][8][9][10]. All publications showed expanded MSC transplantation was safe.…”

Section: Dear Editor-in-chiefmentioning

confidence: 99%

Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion

Salval¹,

Moto

2017

Prog. Stem Cell

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More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment for human diseases. More than five MSCs based stem cell drug products are approved at various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for 5 and 10 years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidences about the safety of expanded MSCs in clinical applications. However, the MSC quality should be stritcly controlled during the in vitro MSC expansion.

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Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

Abstract: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

Cited by 94 publications

References 31 publications

Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy

Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy

Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis: A Meta-Analysis

Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion

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