Various strategies to improve efficacy of stem cell transplantation in multiple sclerosis: Focus on mesenchymal stem cells and neuroprotection

Yousefi, Farzad; Arab, Fahimeh Lavi; Saeidi, Kolsoum; Amiri, Houshang; Mahmoudi, Mahmoud

doi:10.1016/j.jneuroim.2018.11.015

Cited by 27 publications

(20 citation statements)

References 205 publications

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“…The intrathecal administration of the MSC/HSC preparation, containing 4 × 10 5 of CD34 + cells into rats that had been subjected to a spinal cord injury, was shown to improve functional outcomes and decrease peripheral concentrations of pro‐inflammatory cytokines (TNF, IL‐1ß, and IL‐6) in the cerebrospinal fluid . Previous studies have reported beneficial effects of stem cell therapy in animal models of ALS; the majority of these studies employed manipulated MCSs, while the use of unmanipulated stem cells and preparations containing HSCs and MSCs has been shown to increase the therapeutic activity of stem cell therapy . Thus, we hypothesized that this treatment might also ameliorate ALS‐like pathology owing to the anti‐inflammatory effects of Neuro‐Cells.…”

Section: Introductionmentioning

confidence: 99%

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

et al. 2019

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Aims:Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 10 6 mesenchymal and hemopoietic human stem cells, containing 5 × 10 5 of CD34 + cells), which showed antiinflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle.Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Celltreated mutants had reduced muscle atrophy and lumbar motor neuron degeneration.This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion:The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. | 505MUNTER ET al.

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Section: Introductionmentioning

confidence: 99%

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

et al. 2019

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“…Because of its multifocal nature, the therapeutic approach of a MRgFUS stem-cell delivery regiment may be beneficial for disease modifying therapies of MS or for treating acute flares, while other routes such as direct injection may be less optimal (132). Since the clinical management of an MS flare already involves MRI scanning to detect new lesions of immune hyperactivity, an MRgFUS procedure to deliver immunomodulatory MSCs or NSCs to these regions could be seamlessly integrated (133). By combining cell therapies with standard of care, which involve systemic high potency corticosteroids and a tapered course of oral corticosteroids, the high burden of these medications that confer adverse effects (i.e., Cushing's syndrome symptoms of weight gain, impaired wound healing, muscle breakdown) may be reduced (134).…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

et al. 2021

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Stem cell and immune cell therapies are being investigated as a potential therapeutic modality for CNS disorders, performing functions such as targeted drug or growth factor delivery, tumor cell destruction, or inflammatory regulation. Despite promising preclinical studies, delivery routes for maximizing cell engraftment, such as stereotactic or intrathecal injection, are invasive and carry risks of hemorrhage and infection. Recent developments in MRI-guided focused ultrasound (MRgFUS) technology have significant implications for treating focal CNS pathologies including neurodegenerative, vascular and malignant processes. MRgFUS is currently employed in the clinic for treating essential tremor and Parkinson's Disease by producing precise, incisionless, transcranial lesions. This non-invasive technology can also be modified for non-destructive applications to safely and transiently open the blood-brain barrier (BBB) to deliver a range of therapeutics, including cells. This review is meant to familiarize the neuro-interventionalist with this topic and discusses the use of MRgFUS for facilitating cellular delivery to the brain. A detailed and comprehensive description is provided on routes of cell administration, imaging strategies for targeting and tracking cellular delivery and engraftment, biophysical mechanisms of BBB enhanced permeability, supportive proof-of-concept studies, and potential for clinical translation.

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“…Despite findings suggesting nHSCs as promising therapeutic tools for diseases such as PMS in which tissue repair is needed and/or inflammation is extensive, clinical translation of nHSC transplantation has met some barriers. These include limited engraftment duration, little in vivo differentiation, and restricted accessibility into damaged sites (Yousefi et al, 2019). Additionally, the complex functionality of stem cells makes it difficult to clearly correlate their distinct therapeutic mechanisms of action and resultant outcomes in clinical studies.…”

Section: Mechanisms Of Action For Non-hematopoietic Stem Cellsmentioning

confidence: 99%

Stem Cell Therapies for Progressive Multiple Sclerosis

Smith¹,

Nicaise

Ionescu

et al. 2021

Front. Cell Dev. Biol.

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal degeneration. MS patients typically present with a relapsing-remitting (RR) disease course, manifesting as sporadic attacks of neurological symptoms including ataxia, fatigue, and sensory impairment. While there are several effective disease-modifying therapies able to address the inflammatory relapses associated with RRMS, most patients will inevitably advance to a progressive disease course marked by a gradual and irreversible accrual of disabilities. Therapeutic intervention in progressive MS (PMS) suffers from a lack of well-characterized biological targets and, hence, a dearth of successful drugs. The few medications approved for the treatment of PMS are typically limited in their efficacy to active forms of the disease, have little impact on slowing degeneration, and fail to promote repair. In looking to address these unmet needs, the multifactorial therapeutic benefits of stem cell therapies are particularly compelling. Ostensibly providing neurotrophic support, immunomodulation and cell replacement, stem cell transplantation holds substantial promise in combatting the complex pathology of chronic neuroinflammation. Herein, we explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and we discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.

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Various strategies to improve efficacy of stem cell transplantation in multiple sclerosis: Focus on mesenchymal stem cells and neuroprotection

Cited by 27 publications

References 205 publications

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

Stem Cell Therapies for Progressive Multiple Sclerosis

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