Human Umbilical Cord Blood Mesenchymal Stem Cells Reduce Colitis in Mice by Activating NOD2 Signaling to COX2

Kim, Hyung–Sik; Shin, Tae–Hoon; Lee, Byung–Chul; Yu, Kyung–Rok; Seo, Yoojin; Lee, Seung‐Hee; Seo, Min–Soo; Hong, In–Sun; Choi, Soon Won; Seo, Kangmoon; Núñez, Gabriel; Park, Jong–Hwan; Kang, Kyung‐Sun

doi:10.1053/j.gastro.2013.08.033

Cited by 153 publications

(173 citation statements)

References 29 publications

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“…In aged MSCs, proinflammatory stimuli, such as interferon gamma (IFN ) and tumor necrosis factor alpha (TNF ), increased the phosphorylation of the p38 MAPK, and this phosphorylation was associated with the downregulation of cyclooxygenase-2(COX2)/prostaglandin E 2 (PGE 2 ), suggesting the immunomodulatory ability of MSCs gradually declines with consecutive passages via the p38 MAPK alteration of COX2/PGE 2 levels. In agreement with the immunomodulatory function with PGE 2 , MSCs suppress mononuclear cell proliferation and reduce the severity of colitis through the nucleotide-binding oligomerization domain 2 (NOD2) receptor-interacting serine/threonineprotein kinase 2 (RIP2) pathway, leading to the elevation of PGE 2 production (Figure 1) [13].…”

Section: Ros Oxidative Stress and Cellular Signaling In Mscs Agingmentioning

confidence: 59%

Protective Effects of Ellagic Acid against UVA-induced Oxidative Stress in Human Dermal Papilla

Kim¹,

Han²,

An³

et al. 2016

Asian J Beauty Cosmetol

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MSCs have become an emerging cell source with their immune modulation, high proliferation rate, and differentiation potential; indeed, they have been challenged in clinical trials. Recently, it has shown that ROS play a dual role as both deleterious and beneficial species depending on their concentration in MSCs. Various environmental stresses-induced excessive production of ROS triggers cellular senescence and abnormal differentiation on MSCs. Moreover, MSCs have been suggested to participate in the treatment of ALI/ARDS and COPD as a major cause of high morbidity and mortality. Therapeutic mechanisms of MSCs in the treatment of ARDS/COPD were focused on cell engraftment and paracrine action. However, ROS-mediated therapeutic mechanisms of MSCs still remain largely unknown. Here, we review the key factors associated with cell cycle and chromatin remodeling to accelerate or delay the MSC aging process. In addition, the enhanced ROS production and its associated pathophysiological pathways will be discussed along with the MSC senescence process. Furthermore, the present review highlights how the excessive amount of ROS-mediated oxidative stress might interfere with homeostasis of lungs and residual lung cells in the pathogenesis of ALI/ARDS and COPD.

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Section: Ros Oxidative Stress and Cellular Signaling In Mscs Agingmentioning

confidence: 59%

Protective Effects of Ellagic Acid against UVA-induced Oxidative Stress in Human Dermal Papilla

Kim¹,

Han²,

An³

et al. 2016

Asian J Beauty Cosmetol

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show abstract

“…[29][30][31][32][33] In the present study we focused on B cells, MCs, and histamine as major players in MSCmediated EAC immunosuppression pathways. We demonstrated that the addition of specific neutralizing antibodies for IL-10 and TGF-b1 and a specific inhibitor for IDO or NO did not affect MSC-CMT-mediated inhibition of IgE release by B cells, but pretreatment of MSCs with NS398, a specific inhibitor of COX2/PGE 2 , significantly reversed these inhibitory effects on B-cell IgE release.…”

Section: Discussionmentioning

confidence: 99%

Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms

Wan

Huang

et al. 2015

Journal of Allergy and Clinical Immunology

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“…Fluorescence time course traces were analyzed with Origin Pro (version 8.0) traces. The peak amplitude of the 100AP was selected at the end of the stimulation at 10 Hz for 10 s, and the peak of NH 4 Cl was the mean value of the plateau area, as previously described [22].…”

Section: Optical Setup For Cellular Imaging and Data Analysismentioning

confidence: 99%

GDF-15 Secreted from Human Umbilical Cord Blood Mesenchymal Stem Cells Delivered Through the Cerebrospinal Fluid Promotes Hippocampal Neurogenesis and Synaptic Activity in an Alzheimer's Disease Model

Kim

Lee

Chang

et al. 2015

Stem Cells and Development

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Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-b (Ab) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Ab42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD.

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Human Umbilical Cord Blood Mesenchymal Stem Cells Reduce Colitis in Mice by Activating NOD2 Signaling to COX2

Cited by 153 publications

References 29 publications

Protective Effects of Ellagic Acid against UVA-induced Oxidative Stress in Human Dermal Papilla

Protective Effects of Ellagic Acid against UVA-induced Oxidative Stress in Human Dermal Papilla

Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms

GDF-15 Secreted from Human Umbilical Cord Blood Mesenchymal Stem Cells Delivered Through the Cerebrospinal Fluid Promotes Hippocampal Neurogenesis and Synaptic Activity in an Alzheimer's Disease Model

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