A Novel Endogenous Damage Signal, CSF-2, Activates Multiple Beneficial Functions of Adipose Tissue-Derived Mesenchymal Stem Cells

Park, Se-Ra; Cho, Ara; Kim, Jae-Wan; Lee, Hwa-Yong; Hong, In–Sun

doi:10.1016/j.ymthe.2019.03.010

Cited by 25 publications

(25 citation statements)

References 56 publications

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“…It is known as a hematopoietic growth factor involved in the survival, proliferation and differentiation of various myeloid cells from hematopoietic progenitor cells ( 49 ). Recently, it has been reported that it is actively secreted by stem cells, in response to various types of injury ( 50 , 51 ). Our results indicated an increase of 90 folds of CSF2/GM-CSF in EV treated-HSPCs.…”

Section: Discussionmentioning

confidence: 99%

Acute Myeloid Leukemia Cells Functionally Compromise Hematopoietic Stem/Progenitor Cells Inhibiting Normal Hematopoiesis Through the Release of Extracellular Vesicles

et al. 2022

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Acute myeloid leukemia (AML) is an aggressive and heterogeneous clonal disorder of hematopoietic stem/progenitor cells (HSPCs). It is not well known how leukemia cells alter hematopoiesis promoting tumor growth and leukemic niche formation. In this study, we investigated how AML deregulates the hematopoietic process of HSPCs through the release of extracellular vesicles (EVs). First, we found that AML cells released a heterogeneous population of EVs containing microRNAs involved in AML pathogenesis. Notably, AML-EVs were able to influence the fate of HSPCs modifying their transcriptome. In fact, gene expression profile of AML-EV-treated HSPCs identified 923 down- and 630 up-regulated genes involved in hematopoiesis/differentiation, inflammatory cytokine production and cell movement. Indeed, most of the down-regulated genes are targeted by AML-EV-derived miRNAs. Furthermore, we demonstrated that AML-EVs were able to affect HSPC phenotype, modifying several biological functions, such as inhibiting cell differentiation and clonogenicity, activating inflammatory cytokine production and compromising cell movement. Indeed, a redistribution of HSPC populations was observed in AML-EV treated cells with a significant increase in the frequency of common myeloid progenitors and a reduction in granulocyte-macrophage progenitors and megakaryocyte-erythroid progenitors. This effect was accompanied by a reduction in HSPC colony formation. AML-EV treatment of HSPCs increased the levels of CCL3, IL-1B and CSF2 cytokines, involved in the inflammatory process and in cell movement, and decreased CXCR4 expression associated with a reduction of SDF-1 mediated-migration. In conclusion, this study demonstrates the existence of a powerful communication between AML cells and HSPCs, mediated by EVs, which suppresses normal hematopoiesis and potentially contributes to create a leukemic niche favorable to neoplastic development.

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Section: Discussionmentioning

confidence: 99%

Acute Myeloid Leukemia Cells Functionally Compromise Hematopoietic Stem/Progenitor Cells Inhibiting Normal Hematopoiesis Through the Release of Extracellular Vesicles

et al. 2022

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“…Adipose tissue-derived mesenchymal stem cells (ADSCs) are candidates for treating various diseases in the fields of regenerative medicine, because of their multidirectional differentiation potential, immunoregulation, and potent paracrine functions [1, 2]. Until 2018, more than 190 clinical trials of ADSC-based therapy are described in the database of “ClinicalTrials.gov,” and most clinical applications need to implement 10–100 million ADSCs for each therapy [3].…”

Section: Introductionmentioning

confidence: 99%

Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion

et al. 2019

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Background Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising candidates for regenerative medicine. However, long-term in vitro passaging leads to stemness loss and cell senescence of ADSCs, resulting in failure of ADSC-based therapy. Methods In this study, ADSCs were treated with low dose of antioxidants (reduced glutathione and melatonin) with anti-aging and stem cell protection properties in the in vitro passaging, and the cell functions including stem cell senescence, cell migration, cell multidirectional differentiation potential, and ROS content were carefully analyzed. Results We found that GSH and melatonin could maintain ADSC cell functions through reducing cell senescence and promoting cell migration, as well as by preserving stemness and multidirectional differentiation potential, through inhibiting ROS generation during long-term expansion of ADSCs. Conclusions Our results suggested that antioxidant treatment could efficiently prevent the dysfunction and preserve cell functions of ADSCs after long-term passaging, providing a practical strategy to facilitate ADSC-based therapy.

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“…Indeed, GM-CSF has also been shown to play a major role in neuronal plasticity that is critical for learning/memory (108). In addition to its effects on NSCs, GM-CSF has been shown to mobilize mesenchymal stem cells (MSCs) from the bone marrow and to enhance their differentiation and migration in response to injury (109,110). MSCs have been reported to have beneficial cognitive and regenerative effects and are being investigated as potential positive effectors in several neurological disorders, including AD, PD, and spinal cord injury (111)(112)(113)(114)(115)(116)(117).…”

Section: Discussionmentioning

confidence: 99%

Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice

Ahmed

Wang

Elos

et al. 2021

Preprint

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Down syndrome (DS) is characterized by chronic neuroinflammation, peripheral inflammation, astrogliosis, imbalanced excitatory/inhibitory neuronal function, and cognitive deficits in both humans and mouse models. Suppression of inflammation has been proposed as a therapeutic approach to treating DS co-morbidities, including intellectual disability (DS/ID). Conversely, we discovered previously that treatment with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) improved cognition and reduced biomarkers of brain pathology in humans with Alzheimer·s disease (AD), another inflammatory disorder, and in a mouse model of AD. To investigate the effects of GM-CSF treatment on DS/ID, we assessed behavior and brain pathology in 12-14 month-old DS mice (Dp[16]1Yey) and their wild-type (WT) littermates, neither of which develop amyloid, and found that GM-CSF treatment improved performance in the radial arm water maze in both Dp16 and WT mice compared to placebo. Dp16 mice also showed abnormal astrocyte morphology and aggregation and fewer calretinin-positive interneurons, both of which were improved by GM-CSF treatment. These findings suggest that stimulating and/or modulating inflammation and the innate immune system with GM-CSF treatment may enhance cognition in both people with DS/ID and in the typical aging population.

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A Novel Endogenous Damage Signal, CSF-2, Activates Multiple Beneficial Functions of Adipose Tissue-Derived Mesenchymal Stem Cells

Cited by 25 publications

References 56 publications

Acute Myeloid Leukemia Cells Functionally Compromise Hematopoietic Stem/Progenitor Cells Inhibiting Normal Hematopoiesis Through the Release of Extracellular Vesicles

Acute Myeloid Leukemia Cells Functionally Compromise Hematopoietic Stem/Progenitor Cells Inhibiting Normal Hematopoiesis Through the Release of Extracellular Vesicles

Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion

Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice

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