The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

Giacoppo, Sabrina; Bramantı, Placido; Mazzon, Emanuela

doi:10.1007/s00005-017-0460-z

Cited by 20 publications

(12 citation statements)

References 158 publications

(169 reference statements)

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“…Along with immunomodulatory and immunosuppressive roles, the regenerating capability of MSCs make them unique and a very suitable candidate for cell-based therapy in autoimmune and inflammatory disorders [229][230][231]. The differentiation potential of MSCs into IPCs is the most striking of their features, which can be used to ameliorate hyperglycemia.…”

Section: Mechanistic Details Of Mscs With Clinical Trialsmentioning

confidence: 99%

Identifying the Therapeutic Significance of Mesenchymal Stem Cells

Mishra

Shih

Parveen

et al. 2020

Cells

120

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The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.

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Section: Mechanistic Details Of Mscs With Clinical Trialsmentioning

confidence: 99%

Identifying the Therapeutic Significance of Mesenchymal Stem Cells

Mishra

Shih

Parveen

et al. 2020

Cells

120

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“…Hepatocyte growth factor (HGF) secreted by MSCs was responsible for the beneficial effects of MSCs [13]. Other neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell derived neurotrophic factor (GDNF), which were released by MSCs have also been demonstrated useful in promoting function recovery in MS [14,15]. Consequently, MSCs transplantation not only alleviated function disability through immune-regulating ability, but also promoted function recovery through the release of trophic factors.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice

Liu

et al. 2020

Mol Neurobiol

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Blood-brain barrier disruption is one of the hallmarks of multiple sclerosis. Mesenchymal stem cells showed great potential for the multiple sclerosis therapy. However, the effect of mesenchymal stem cells on blood-brain barrier in multiple sclerosis remains unclear. Here, we investigated whether mesenchymal stem cells transplantation protected blood-brain barrier integrity and further explored possible underlying mechanisms. Adult female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptide33-55 (MOG33-55) to induce experimental autoimmune encephalomyelitis (EAE). Mesenchymal stem cells (5 × 10 5) were transplanted via tail vein at disease onset. In the cell culture, we examined lipopolysaccharide-induced AQP4 upregulation in astrocytes. Results indicated that mesenchymal stem cells therapy improved neurobehavioral outcomes in EAE mice, reduced inflammatory cell infiltration, IgG protein leakage, and demyelination in spinal cord. Mesenchymal stem cells therapy also increased tight junction protein expression. In addition, mesenchymal stem cells downregulated AQP4 and A 2B adenosine receptor (A 2B AR) expression in EAE mice in spinal cord. We found that MSCs-conditioned medium (MCM) reduced the expression of inflammatory cytokines, AQP4 and A 2B AR in lipopolysaccharide-activated astrocytes. BAY-60-6583 (a selective A 2B AR agonist) reversed the MCM-induced AQP4 downregulation and increased p38 MAPK phosphorylation. Furthermore, the upregulation effects of A 2B AR agonist were eliminated when treated with p38 MAPK inhibitor SB203580. Thus, we concluded that mesenchymal stem cells alleviated blood-brain barrier disruption by downregulating AQP4 in multiple sclerosis, possibly through inhibiting the A 2B AR/p38 MAPK signaling pathway. Our work suggests that mesenchymal stem cells exert beneficial effect through maintaining blood-brain barrier integrity in EAE mice.

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confidence: 99%

“…Thus, the discovery of innovative approaches to improve outcomes for patients with MS is an objective of primary importance. In this context, a wide range of secreted factors that are produced by mesenchymal stem cells (MSCs), including growth factors, chemokines, and cytokines, which are generally defined as the MSC secretome, has shown great potential for the treatment of MS (4)(5)(6). In particular, neural crest MSCs from human dental tissues, such as periodontal ligament, dental pulp, and gingiva, received considerable interest because of the ABBREVIATIONS: BDNF, brain derived neurotrophic factor; CM, conditioned medium; EAE, experimental autoimmune encephalomyelitis; H-hPDLSCs-CM, conditioned medium from human periodonal ligament stem cells under hypoxia; hPDLSC, human periodontal ligament stem cell; HRP, horseradish peroxidase; MBP, myelin basic protein; MOG , myelin oligodendroglial glycoprotein peptide; MS, multiple sclerosis; MSC, mesenchymal stem cell; mTOR, mammalian target of rapamycin; NT3, neurotrophin-3; T h , T helper minimal invasive procedure involved in their collection, the remarkable differentiation ability to neurogenic and other cell lineages, economical cost, and the freedom from ethical concerns (7)(8)(9).…”

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confidence: 99%

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Giacoppo

Rajan

Diomede³

et al. 2017

The FASEB Journal

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Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed the secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) from human periodontal ligament stem cells (hPLSCs) under hypoxia (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35–55. At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice. Our results demonstrate the efficacy of H-hPDLSCs-CM treatment in diminishing clinical and histologic disease score. A key finding from this study is the marked expression of anti-inflammatory cytokine IL-37, paralleled by the suppression of proinflammatory cytokines in mice with EAE that were treated with H-hPDLSCs-CM. In addition, a consequent modulation of oxidative stress, autophagic, and apoptotic markers was observed in mice with EAE after hPDLSCs-CM administration. In addition, to provide additional evidence of the molecular mechanisms that underlie H-hPDLSCs-CM, we investigated its therapeutic action in scratch injury–exposed NSC-34 neurons, an in vitro model of injury. This model reproduces severe inflammation and oxidative stress conditions as observed after EAE damage. In vitro results corroborate the ability of hPDLSCs-CM to modulate inflammatory, oxidative stress, and apoptotic pathways. Taken together, our findings suggest H-hPDLSCs-CM as a new pharmacologic opportunity for the management of MS.—Giacoppo, S., Thangavelu, S. R., Diomede, F., Bramanti, P., Conti, P., Trubiani, O., Mazzon, E. Anti-inflammatory effects of hypoxia-preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL-37.

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The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

Cited by 20 publications

References 158 publications

Identifying the Therapeutic Significance of Mesenchymal Stem Cells

Identifying the Therapeutic Significance of Mesenchymal Stem Cells

Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

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