Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease

Mita, T.; Furukawa‐Hibi, Yoko; Takeuchi, Hideyuki; Hattori, Hiroyuki; Yamada, Kiyofumi; Hibi, Hideharu; Ueda, Minoru; Yamamoto, Akihito

doi:10.1016/j.bbr.2015.07.043

Cited by 139 publications

(136 citation statements)

References 65 publications

(92 reference statements)

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“…When reached 90% confluence, MSCs passage 2 were washed 3 times with phosphate-buffered saline (PBS) and seeded at 1×10 4 cells/ml in 24-well plates containing serum-free DMEM (14). Each 24-well plate was divided equally (12 wells) into CM and CM-Sal in which the latter was exposed to 100 μ g/mL salidroside (purity ≥95% (LC/MS-ELSD), Sigma–Aldrich, MO, USA) for 48 h of culture (10).…”

Section: Methodsmentioning

confidence: 99%

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Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation- Histological and Immunohistochemical Study

Maadawi

2017

IJSC

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Background and ObjectivesNeuroinflammation is involved in the pathogenesis of neurodegenerative disorders. Conditioned medium (CM) derived from bone marrow mesenchymal stem cells (MSCs) revealed substantial benefits due to its rich content of trophic factors. Salidroside (Sal), extracted from Rhodiola rosea, is known for its anti-inflammatory and neuroprotective effects. This study was designed to investigate the effect of Sal pretreated CM (CM-Sal) derived from bone marrow MSCs in lipopolysaccharide (LPS) induced neuroinflammation.Material and MethodsFifty adult male mice were equally divided into 5 groups: Group I (Normal Control), Group II (LPS): single 0.8 mg/kg LPS intraperitoneally; Group III (LPS-DMEM), Group IV (LPS-CM) and Group V (LPS-CM-Sal): LPS was injected as group II followed, 24 hours later, by intranasal injection of 50 μl of filtered serum-free Dulbecco’s Modified Eagle’s medium (DMEM), CM or CM-Sal, respectively, twice daily for 4 days. Animals were sacrificed at day 6 and paraffin cerebral sections were subjected to Hematoxylin and Eosin staining and immunohistochemistry with caspase 3 (apoptosis), glial fibrillary acidic protein GFAP (astrocytes) and CD68 (active microglia) followed by quantitative morphometric study.ResultsExamination of LPS and LPS-DMEM groups revealed neuronal apoptosis with reactive astrogliosis and increased active microglia. LPS-CM and LPS-CM-Sal groups showed less apoptosis, less astrocytes and less active microglia. The regression in neuroinflammation was more evident in LPS-CM-Sal group and the difference was statistically significant compared to other groups.ConclusionCM-Sal derived from MSCs culture elicited significant histopathological improvement in LPS induced neuroinflammation which could be used as new therapeutic modality.

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Section: Methodsmentioning

confidence: 99%

“…Twenty four hours later, animals were subjected to intranasal injection of 50 μ l of CM twice daily for 4 days (14). …”

Section: Methodsmentioning

confidence: 99%

Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation- Histological and Immunohistochemical Study

Maadawi

2017

IJSC

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“…We showed previously that SHED-CM improved a rodent model of spinal cord injury, liver inflammation, lung fibrosis, rheumatoid arthritis, and Alzheimer's disease by inducing macrophage phenotype conversion from M1 to M2 (19)(20)(21)(22)(23). SHED-CM contains a set of M2-inducing molecules, including MCP-1 and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), which promote functional recovery from spinal cord injury (23).…”

Section: Ultiple Sclerosis (Ms) and Its Animal Model Experimental mentioning

confidence: 99%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

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Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the CNS. Current MS treatments, including immunomodulators and immunosuppressants, do not result in complete remission. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells derived from dental pulp. Both SHED and SHED-conditioned medium (SHED-CM) exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. In this study, we investigated the efficacy of SHED-CM in treating experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE mice treated with a single injection of SHED-CM exhibited significantly improved disease scores, reduced demyelination and axonal injury, and reduced inflammatory cell infiltration and proinflammatory cytokine expression in the spinal cord, which was associated with a shift in the microglia/macrophage phenotype from M1 to M2. SHED-CM also inhibited the proliferation of myelin oligodendrocyte glycoprotein–specific CD4+ T cells, as well as their production of proinflammatory cytokines in vitro. Treatment of EAE mice with the secreted ectodomain of sialic acid–binding Ig-like lectin-9, a major component of SHED-CM, recapitulated the effects of SHED-CM treatment. Our data suggest that SHED-CM and secreted ectodomain of sialic acid–binding Ig-like lectin-9 may be novel therapeutic treatments for autoimmune diseases, such as MS.

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“…They have found that SHED-derived, serum-free Conditioned Medium (SHED-CM) improved cognitive function in an Alzheimer's disease mouse model [158] and enhanced recovery of focal cerebral ischemia in rats after intranasal administration [159]. Additionally, SHED-CM after intracerebral administration in mice with perinatal hypoxia-ischemia-induced brain injury generated an anti-inflammatory environment, reduced tissue loss, and significantly improved the neurological outcome by converting a M1 proinflammatory to an M2 anti-inflammatory environment.…”

Section: Differentiation Potential and Paracrine Activity Of Dentamentioning

confidence: 99%

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

Bakopoulou

About

2016

Stem Cells International

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Dental Mesenchymal Stem Cells (MSCs), including Dental Pulp Stem Cells (DPSCs), Stem Cells from Human Exfoliated Deciduous teeth (SHED), and Stem Cells From Apical Papilla (SCAP), have been extensively studied using highly sophisticated in vitro and in vivo systems, yielding substantially improved understanding of their intriguing biological properties. Their capacity to reconstitute various dental and nondental tissues and the inherent angiogenic, neurogenic, and immunomodulatory properties of their secretome have been a subject of meticulous and costly research by various groups over the past decade. Key milestone achievements have exemplified their clinical utility in Regenerative Dentistry, as surrogate therapeutic modules for conventional biomaterial-based approaches, offering regeneration of damaged oral tissues instead of simply “filling the gaps.” Thus, the essential next step to validate these immense advances is the implementation of well-designed clinical trials paving the way for exploiting these fascinating research achievements for patient well-being: the ultimate aim of this ground breaking technology. This review paper presents a concise overview of the major biological properties of the human dental MSCs, critical for the translational pathway “from bench to clinic.”

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Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease

Cited by 139 publications

References 65 publications

Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation- Histological and Immunohistochemical Study

Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation- Histological and Immunohistochemical Study

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

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