Repeat Administration of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment of Amyotrophic Lateral Sclerosis

Siwek, Tomasz; Jezierska-Woźniak, Katarzyna; Maksymowicz, Stanisław; Barczewska, Monika; Sowa, Mariusz; Badowska, Wanda; Maksymowicz, Wojciech

doi:10.12659/msm.927484

Cited by 26 publications

(18 citation statements)

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“…( Mazzini et al, 2010 ). Repetitive injections of cells have commonly been used in cellular therapy; for example, repeated injections of autologous bone marrow-derived MSCs (BM-MSCs) are showing no significant adverse events ( Nabavi et al, 2019 ; Siwek et al, 2020 ). A phase II clinical trial with repeated intrathecal administration of BM-MSCs in patients with ALS is safe and well-tolerated ( Petrou et al, 2021 ).…”

Section: Cellular Therapymentioning

confidence: 99%

“…The preparation of BM-MSCs for patients with rapid disease progression is challenging and time-consuming. Thus, other allogeneic sources of MSCs should be identified for this type of therapy ( Siwek et al, 2020 ). Moreover, immunomodulatory effects of ALS patient-derived MSCs are reduced due to their higher levels of pro-inflammatory cytokines.…”

Section: Cellular Therapymentioning

confidence: 99%

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Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Lin

Cheng

et al. 2022

Front. Cell Dev. Biol.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for ALS is currently available. In recent years, cellular therapy has shown considerable therapeutic potential because it exerts immunomodulatory effects and protects the MN circuit. However, the safety and efficacy of cellular therapy in ALS are still under debate. In this review, we summarize the current progress in cellular therapy for ALS. The underlying mechanism, current clinical trials, and the pros and cons of cellular therapy using different types of cell are discussed. In addition, clinical studies of mesenchymal stem cells (MSCs) in ALS are highlighted. The summarized findings of this review can facilitate the future clinical application of precision medicine using cellular therapy in ALS.

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Section: Cellular Therapymentioning

confidence: 99%

Section: Cellular Therapymentioning

confidence: 99%

Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Lin

Cheng

et al. 2022

Front. Cell Dev. Biol.

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Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

“…Mesenchymal stem cells' therapeutic potential has been investigated for the treatment of several neurodegenerative diseases, such as Alzheimer's disease, Amyotrophic Lateral Sclerosis, Multiple sclerosis, Parkinson's disease, polyglutamine (PolyQ) Spinocerebellar ataxias and Leukodystrophies, obtaining encouraging results. 6,18,19,33,[36][37][38][39][40][41][42][43][44][45][46][47][48][49] At the pre-clinical level, MSC have been found to promote tissue regeneration, repair and turnover, by increasing cell survival and neurogenesis, inhibiting apoptosis, favouring abnormal aggregate clearance and modulating the immune system, through their paracrine activity. 5,8,47,[50][51][52][53][54][55][56][57][58] Indeed, MSC can "sense" the environment created by the signals emitted by injured tissues and home to target areas where they secrete an array of molecules, including cytokines/chemokines and neurotrophic factors.…”

Section: Therapeutic Outcomes In Neurological Contextmentioning

confidence: 99%

Mesenchymal stem cells for lysosomal storage and polyglutamine disorders: Possible shared mechanisms

Miranda

2021

Eur J Clin Investigation

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Background Mesenchymal stem cells' (MSC) therapeutic potential has been investigated for the treatment of several neurodegenerative diseases. The fact these cells can mediate a beneficial effect in different neurodegenerative contexts strengthens their competence to target diverse mechanisms. On the other hand, distinct disorders may share similar mechanisms despite having singular neuropathological characteristics. Methods We have previously shown that MSC can be beneficial for two disorders, one belonging to the groups of Lysosomal Storage Disorders (LSDs) – the Krabbe Disease or Globoid Cell Leukodystrophy, and the other to the family of Polyglutamine diseases (PolyQs) – the Machado‐Joseph Disease or Spinocerebellar ataxia type 3. We gave also input into disease characterization since neuropathology and MSC's effects are intrinsically associated. This review aims at describing MSC's multimode of action in these disorders while emphasizing to possible mechanistic alterations they must share due to the accumulation of cellular toxic products. Results Lysosomal storage disorders and PolyQs have different aetiology and associated symptoms, but both result from the accumulation of undegradable products inside neuronal cells due to inefficient clearance by the endosomal/lysosomal pathway. Moreover, numerous cellular mechanisms that become compromised latter are also shared by these two disease groups. Conclusions Here, we emphasize MSC's effect in improving proteostasis and autophagy cycling turnover, neuronal survival, synaptic activity and axonal transport. LSDs and PolyQs, though rare in their predominance, collectively affect many people and require our utmost dedication and efforts to get successful therapies due to their tremendous impact on patient s' lives and society.

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“…Few small, mostly open-label, clinical trials have reported indications of favorable effects of MSC treatment in neurological diseases, such as stroke, multi-system atrophy, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. Specifically, in ALS, the first phase I/II trial from our group, in which 19 patients received both intrathecal and intravenous injections of MSC, showed that this combined administration was safe, in the short term follow up and induced a trend for stabilization of disease progression during the 6 months following transplantation [37].…”

Section: Introductionmentioning

confidence: 99%

A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis

Petrou

Kassis

Yaghmour

et al. 2021

Front. Biosci. (Landmark Ed)

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Background: Mesenchymal stem cells (MSC) were shown to induce beneficial effects in animal models of neurodegeneration and in pilot human trials in multiple sclerosis and amyotrophic lateral sclerosis (ALS). Aim: An open-label, clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous-MSC in ALS-patients. Methods: The study included 20 subjects (age: 20–70) with definite diagnosis of ALS and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score of >20. The patients were treated with 1–4 intrathecal injections of MSC, at intervals of 3–6 months. The primary endpoints were safety and tolerability. Efficacy measurements including ALSFRS-R score and forced vital capacity (FVC), were assessed as secondary endpoints. Results: No serious adverse events were observed during the whole period of the trial. One patient withdrew from the study before the first injection. The monthly rate of progression in ALSFRS-R was ameliorated by more than 25% in 15/19 patients between the 1st and 2nd injection (mean improvement of 107.1%); in 11/12 between the 2nd and 3rd injection and in 8/10 between the 3rd and 4th injection. Overall, during the whole period till the last transplantation 13 patients had a >25% improvement in the slope of progression of ALSFRS-R (mean improvement of 47.4%, p < 0.0038, Wilcoxon rank signed test). 7 out of 19 patients actually improved clinically (range of increase in ALSFRS-R: +1 to +4 degrees) after the first transplantation and 5 remained improved after the second cycle. The response rate correlated with the time-intervals between the injections. Conclusion: The results of our study show that repeated intrathecal injections of autologous MSC was safe in patients with ALS and provide indications of medium-term clinical benefits that were related to the intervals between the administrations of the cells. Larger studies are needed to confirm these observations.

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Repeat Administration of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment of Amyotrophic Lateral Sclerosis

Cited by 26 publications

References 0 publications

Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Mesenchymal stem cells for lysosomal storage and polyglutamine disorders: Possible shared mechanisms

A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis

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