Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

Harris, Violaine K.; Yan, Qi; Vyshkina, Tamara; Sahabi, Sadia; Liu, Xinhe; Sadiq, Saud

doi:10.1016/j.jns.2011.08.036

Cited by 113 publications

(106 citation statements)

References 35 publications

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“…Recently, MSCs have been the focus of intensive investigations because of their relative advantages (22)(23)(24). The generation of MSC-NPCs from hUCB-MSCs can be used for basic research in order to develop effective cells for regenerative therapy (11). In addition, recent reports have documented that MSCs can differentiate into MSC-NPCs (16,17).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, more attention has been paid to MSCderived NPCs (MSC-NPCs) for the treatment of neurodegenerative diseases (10)(11)(12)(13). To date, it has been reported that MSCs could induce neural differentiation through many in vitro methods, such as chemical inducers, growth factors, and co-cultures with neural cells (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Neural Differentiation of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells

Rafieemehr¹,

Kheirandish²,

Soleimani³

2016

Avicenna J Med Biochem

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neural Differentiation of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells

Rafieemehr¹,

Kheirandish²,

Soleimani³

2016

Avicenna J Med Biochem

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“…MSCs are thought to function through a 'hit-and-run' mechanism whereby they release an array of cytokines, trophic factors and microvesicles before being rapidly cleared with no significant engraftment [7]. Under conditions of chronic autoimmunity and CNS injury, multiple doses of MSCs are likely to be necessary for the sustained production of immuno modulatory and trophic factors in order to exceed a therapeutic threshold [8,9].…”

mentioning

confidence: 99%

“…In attempting to develop a stem cell-based reparative therapy for MS we are investigating the feasibility of autologous MSC-derived neural progenitors (MSC-NPs) administered in three intrathecal doses spaced 3 months apart [8]. MSCNPs represent a neural subpopulation of MSCs with reduced pluripotency and minimized risk of ectopic differentiation, thus are likely to be more suitable for CNS delivery [8,19].…”

mentioning

confidence: 99%

“…MSCNPs represent a neural subpopulation of MSCs with reduced pluripotency and minimized risk of ectopic differentiation, thus are likely to be more suitable for CNS delivery [8,19]. Importantly, characterization of MSC-NPs established the retention of immunoregulatory and trophic properties associated with MSCs, and MSC-NPs derived from MS and non-MS patients alike were therapeutically viable [19].…”

mentioning

confidence: 99%

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Stem Cell Therapy in Multiple Sclerosis: A Future Perspective

Harris

Sadiq

2015

Neurodegener. Dis. Manag.

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Adenosine A2A receptor agonist ameliorates EAE and correlates with Th1 cytokine‐induced blood brain barrier dysfunction via suppression of MLCK signaling pathway

Liu

Alahiri

Ulloa

et al. 2017

Immunity Inflam & Disease

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IntroductionMultiple sclerosis (MS) disease activity is associated with blood‐brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo.MethodsA2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35–55, and human MS brain. F‐actin and the tight junction protein Claudin‐5 were assessed in endothelial cells treated with an A2A receptor specific agonist (CGS‐21680) after Th1 cytokine stimulation. EAE mice were divided into control and CGS‐21680 (50 µg/kg, i.p., daily) groups. Disease scores were recorded daily to evaluate neurological impairment. The effects of A2A receptor on inflammation and demyelination were assessed after euthanasia by immunostaining or histology; BBB permeability was measured by sodium fluoride (Na‐F) and FITC‐dextran amounts.ResultsEndothelial A2A receptor was detected in demyelination areas of MS brain samples. In EAE lesions, A2A receptor was expressed in the endothelium in association with immune cell infiltration. Treatment with CGS‐21680 counteracted the effects of Th1 cytokines on endothelial cells in vitro, preventing the reduction of tight junction protein expression and stress fiber formation. The effects of A2A receptor activation were correlated with MLCK phosphorylation signaling repression. In EAE, A2A receptor agonist decreased BBB permeability and inhibited EAE neurologic deficiency in mice.ConclusionsA2A receptor activation at EAE onset helps reduce the effects of Th1 stimulation on BBB permeability, indicating that A2A receptor mediates BBB function in CNS demyelinated disease.

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Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

Cited by 113 publications

References 35 publications

Neural Differentiation of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells

Neural Differentiation of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells

Stem Cell Therapy in Multiple Sclerosis: A Future Perspective

Adenosine A2A receptor agonist ameliorates EAE and correlates with Th1 cytokine‐induced blood brain barrier dysfunction via suppression of MLCK signaling pathway

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