Aberrant Expression of COX-2 and FOXG1 in Infrapatellar Fat Pad-Derived ASCs from Pre-Diabetic Donors

O'Donnell, Benjamen; Monjure, Tia A.; Al-Ghadban, Sara; Ives, Clara J.; L'Ecuyer, Michael P; Rhee, Claire; Romero-López, Mónica; Li, Zhong; Goodman, Stuart B.; Lin, Hang; Tuan, Rocky S.; Bunnell, Bruce A.

doi:10.3390/cells11152367

Cited by 7 publications

(8 citation statements)

References 61 publications

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“…In regard to obesity, increased body weight leads to impaired glucose tolerance that results in DM progression [14][15][16][17][18][19][20][21][22][23][24]. Obesity can especially increase the risk of developing DM in young individuals and can affect stem cell proliferation, aging, inflammation, oxidative stress injury, and mitochondrial function [25][26][27][28][29][30][31][32][33][34].…”

Section: Cellular Metabolism Dysfunctionmentioning

confidence: 99%

“…DM can result in insulin resistance and dementia that occurs in patients with AD [84,98,99]. DM can affect impact stem cell proliferation [7,[32][33][34]100], cytoprotective pathways [22,29,98,[101][102][103], retinal disease [38,[104][105][106], and immune-mediated pathways that involve microglia [95,[106][107][108][109][110][111]. Furthermore, over seventy percent of diabetic individuals can develop peripheral neuropathy.…”

Section: Cellular Metabolism In the Nervous Systemmentioning

confidence: 99%

“…In some cases, if the disorder is recognized early in the course of the disease, neurodegenerative disability may be limited. Effective and timely treatment may inhibit both the progression of DM and diseases of the nervous system, such as cognitive loss [26,28,33,52,69,70,84,94,104,120,127,[131][132][133][134][135][136][137][138][139]. Although the use of current pharmaceuticals and diet modification can assist in the treatment of DM and metabolic disorders to prevent hyperglycemic events, these strategies have potential risks that can decrease organ mass, affect cellular organelles, and lead to neuronal loss through processes that involve autophagy [104,124,140,141].…”

Section: New Treatment Strategies To Address Cellular Metabolism Dysf...mentioning

confidence: 99%

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Maiese

2023

Biomolecules

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It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer’s disease (AD) and DM, promote healthy aging, facilitate clearance of β-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.

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Section: Cellular Metabolism Dysfunctionmentioning

confidence: 99%

Section: Cellular Metabolism In the Nervous Systemmentioning

confidence: 99%

Section: New Treatment Strategies To Address Cellular Metabolism Dysf...mentioning

confidence: 99%

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Maiese

2023

Biomolecules

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“…Given that mammalian forkhead transcription factors (FoxOs) can have an important relationship to cell death pathways during neurodegenerative disorders [2,5,49,259,260,[299][300][301][302][303][304], they are increasingly being recognized as potential therapeutic targets for MS (Figure 1). In particular, the mammalian FOXO proteins of the O class can lead to neuronal cell death through apoptosis and autophagy activation [5,49,50,68,128,203,250,301,[305][306][307][308][309][310][311][312][313][314][315].…”

Section: Mammalian Forkhead Transcription Factors and Multiple Sclerosismentioning

confidence: 99%

Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in the nervous system with increased prevalence over the last five decades, and is now being recognized as one significant etiology of cognitive loss and dementia. Presently, disease modifying therapies can limit the rate of relapse and potentially reduce brain volume loss in patients with MS, but unfortunately cannot prevent disease progression or the onset of cognitive disability. Innovative strategies are therefore required to address areas of inflammation, immune cell activation, and cell survival that involve novel pathways of programmed cell death, mammalian forkhead transcription factors (FoxOs), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and associated pathways with the apolipoprotein E (APOE-ε4) gene and severe acute respiratory syndrome coronavirus (SARS-CoV-2). These pathways are intertwined at multiple levels and can involve metabolic oversight with cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into the mechanisms of these pathways can provide new avenues of discovery for the therapeutic treatment of dementia and loss in cognition that occurs during MS.

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“…The biological and functional characteristics of MSCs, isolated from patients with diabetes mellitus, comprising phenotype, proliferation, survival, differentiation, angiogenic potential, and fibrinolytic activity, have been studied, documenting controversial data (Mahmoud et al 2019 ). A number of studies explored the impact of obesity (Table 2 ) (Eljaafari et al 2015 ; Strong et al 2016 ; Serena et al 2016 ; Usha Shalini et al 2017 ; Harrison et al 2020 ; Zhu et al 2021 ; Juntunen et al 2021 ), T2D (Mancini et al 2017 ; Aliakbari et al 2019 ; Wang et al 2020 ; Abu-Shahba et al 2021 ; O’Donnell et al 2022 ), or both (Serena et al 2016 ; Mahmoud et al 2023 ) (Table 3 ) on the immunomodulatory properties of hASCs. Inconsistent results, from being intact (Usha Shalini et al 2017 ; Wang et al 2020 ; Juntunen et al 2021 ) to slightly affected (Mahmoud et al 2023 ), or severely altered (Eljaafari et al 2015 ; Strong et al 2016 ; Serena et al 2016 ; Mancini et al 2017 ; Aliakbari et al 2019 ; Harrison et al 2020 ; Abu-Shahba et al 2021 ; Zhu et al 2021 ) immunoregulatory properties of hASCs from patients with obesity and/or T2D, have been reported, and are illustrated in more detail below.…”

Section: Impact Of Obesity and T2d On Hasc Immunoregulatory Propertiesmentioning

confidence: 99%

Influence of type 2 diabetes and obesity on adipose mesenchymal stem/stromal cell immunoregulation

Mahmoud

Abdel-Rasheed

2023

Cell Tissue Res

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Type 2 diabetes (T2D), associated with obesity, represents a state of metabolic inflammation and oxidative stress leading to insulin resistance and progressive insulin deficiency. Adipose-derived stem cells (ASCs) are adult mesenchymal stem/stromal cells identified within the stromal vascular fraction of adipose tissue. These cells can regulate the immune system and possess anti-inflammatory properties. ASCs are a potential therapeutic modality for inflammatory diseases including T2D. Patient-derived (autologous) rather than allogeneic ASCs may be a relatively safer approach in clinical perspectives, to avoid occasional anti-donor immune responses. However, patient characteristics such as body mass index (BMI), inflammatory status, and disease duration and severity may limit the therapeutic utility of ASCs. The current review presents human ASC (hASC) immunoregulatory mechanisms with special emphasis on those related to T lymphocytes, hASC implications in T2D treatment, and the impact of T2D and obesity on hASC immunoregulatory potential. hASCs can modulate the proliferation, activation, and functions of diverse innate and adaptive immune cells via direct cell-to-cell contact and secretion of paracrine mediators and extracellular vesicles. Preclinical studies recommend the therapeutic potential of hASCs to improve inflammation and metabolic indices in a high-fat diet (HFD)-induced T2D disease model. Discordant data have been reported to unravel intact or detrimentally affected immunomodulatory functions of ASCs, isolated from patients with obesity and/or T2D patients, in vitro and in vivo. Numerous preconditioning strategies have been introduced to potentiate hASC immunomodulation; they are also discussed here as possible options to potentiate the immunoregulatory functions of hASCs isolated from patients with obesity and T2D.

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Aberrant Expression of COX-2 and FOXG1 in Infrapatellar Fat Pad-Derived ASCs from Pre-Diabetic Donors

Cited by 7 publications

References 61 publications

Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Cognitive Impairment in Multiple Sclerosis

Influence of type 2 diabetes and obesity on adipose mesenchymal stem/stromal cell immunoregulation

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