Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr−/− mice

Takafuji, Yoshimasa; Hori, Mika; Mizuno, Toshihide; Harada‐Shiba, Mariko

doi:10.1093/cvr/cvy271

Cited by 55 publications

(68 citation statements)

References 40 publications

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“…Co-culturing of BM-MSCs with IFN-γ/LPS-stimulated BM-derived MΦs (BMDMs) significantly decreased the mRNA levels of M1 markers while enhanced the induction of IL-10 in IL-4-activated BMDMs, suggesting that MSCs switch MΦs from M1 to M2 phenotype [46]. Murine ADSC-CM and ADSC-CM supernatant decreased the expression of M1 markers in both LPS-stimulated and unstimulated BMDMs while it increased the expression of M2 markers in unstimulated BMDMs [47]. ADSC-CM exerted paracrine actions on differentiated human monocyte-derived MΦs to potentiate anti-inflammatory cytokines while it simultaneously reduced the pro-inflammatory cytokine TNFα [17].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Conditioned Media of Stem Cells Derived from Lipoma and Adipose Tissue on Macrophages’ Response and Wound Healing in Indirect Co-culture System In Vitro

Stojanović

Najman

2019

IJMS

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Immunomodulatory and wound healing activities of adipose-derived stem cells (ADSCs) have been reported in various in vitro and in vivo experimental models suggesting their beneficial role in regenerative medicine and treatments of inflammatory-related disorders. Lipoma-derived stem cells (LDSCs) were reported as a potential tool in regenerative medicine due to the similarity with ADSCs but we have previously shown that LDSCs have different differentiation capacity than ADSCs despite a similar mesenchymal phenotype. To further analyze the potential differences and/or similarities between those two stem cell types, in the present study we examined the macrophages (MΦs)’ response, immunomodulatory and wound healing effect of conditioned media (CM) of LDSCs and ADSCs in indirect co-culture system in vitro. We confirmed similar mesenchymal phenotype and stemness state of LDSCs and ADSCs but indicated differences in expression of some inflammatory-related genes. Anti-inflammatory potential of CM of LDSCs and ADSCs, with pronounced effect of LDSCs, in unstimulated RAW 264.7 MΦs was evaluated by decrease in Tnf and increase in Il10 gene expression, which was confirmed by corresponding cytokines’ secretion analysis. Conditioned media of both LDSCs and ADSCs led to the functional activation of MΦs, with slightly more pronounced effect of CM of LDSCs, while both stimulated wound healing in vitro in a similar manner. Results of this study suggest that LDSCs secrete soluble factors like ADSCs and therefore may have a potential for application in regenerative medicine, due to immunomodulatory and wound healing activity, and indicate that LDSCs through secretome may interact with other cells in lipoma tissue.

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Section: Discussionmentioning

confidence: 99%

The Effect of Conditioned Media of Stem Cells Derived from Lipoma and Adipose Tissue on Macrophages’ Response and Wound Healing in Indirect Co-culture System In Vitro

Stojanović

Najman

2019

IJMS

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“…To balance the level of plasma cholesterol, cholesterol in VSMCs, monocytes, macrophages, or hepatocytes is usually absorbed through LDLR [60]. LDLR −/− mice with administration of high-fat diet (HFD) showed cholesterol accumulation in macrophages on the blood vessel wall [61]. However, by treating with exosomes isolated from supernatants of macrophages exposed to lipopolysaccharides, hepatocytes are in the state of inflammation through the LDLR pathway.…”

Section: Exosomes and Lipid Transportationmentioning

confidence: 99%

The crosstalk: exosomes and lipid metabolism

et al. 2020

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Exosomes have been considered as novel and potent vehicles of intercellular communication, instead of "cell dust". Exosomes are consistent with anucleate cells, and organelles with lipid bilayer consisting of the proteins and abundant lipid, enhancing their "rigidity" and "flexibility". Neighboring cells or distant cells are capable of exchanging genetic or metabolic information via exosomes binding to recipient cell and releasing bioactive molecules, such as lipids, proteins, and nucleic acids. Of note, exosomes exert the remarkable effects on lipid metabolism, including the synthesis, transportation and degradation of the lipid. The disorder of lipid metabolism mediated by exosomes leads to the occurrence and progression of diseases, such as atherosclerosis, cancer, nonalcoholic fatty liver disease (NAFLD), obesity and Alzheimer's diseases and so on. More importantly, lipid metabolism can also affect the production and secretion of exosomes, as well as interactions with the recipient cells. Therefore, exosomes may be applied as effective targets for diagnosis and treatment of diseases.

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“…1). Growing body of evidence has demonstrated that allogenic BMSC transplantation can stabilize the plaque via altering immune cellular components within atherosclerotic plaque to alleviate inflammation [24][25][26][27][28]. Being similar to the immunomodulatory effects during the cardiac remodeling process as described above, in the pathogenesis of atherosclerotic plaque, BMSCs increased the ratio of Tregs over CD4 + T cells and promoted the macrophage differentiation towards the M2 phenotype, thereby reducing the monocyte infiltration and inflammatory response [26].…”

Section: Immuno-and Inflammatory Modulation By Bmscs Therapy In Asmentioning

confidence: 86%

“…TNF-α-stimulated ECs up-expressed cell adhesion molecules (CAMs), a factor that can promote monocyte/ macrophage recruitment and adhesion, to initiate the occurrence of AS [44]. It has been shown that when ECs were co-cultured with conditional supernatant or purified exosomes derived from BMSCs, HGF within the exosomes can inhibit CAM production by ECs via downregulating mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways, thereby reducing the recruitment of macrophages [24].…”

Section: The Role Of Allogeneic Bmscs On Ecsmentioning

confidence: 99%

The involving progress of MSCs based therapy in atherosclerosis

2020

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Atherosclerosis is a chronic progressive vascular inflammation characterized by lipid deposition and plaque formation, for which vascular cell dysfunction and impaired immune responses are involved. Up to now, lipidlowering drugs remain the main therapy for treating atherosclerosis; however, the surgical or interventional therapy is often applied, and yet, morbidity and mortality of such cardiovascular disease remain high worldwide. Over the past decades, an anti-inflammatory approach has become an important therapeutic target for dealing with atherosclerosis, as altered immune responses have been regarded as an essential player in the pathological process of vascular abnormality induced by hyperlipidemia. Interestingly, mesenchymal stem cells, one type of stem cells with the capabilities of self-renewal and multi-potential, have demonstrated their unique immunomodulatory function in the various pathological process, especially in atherosclerosis. While some controversies remain regarding their therapeutic efficacy and working mechanisms, our present review aims to summarize the current research progress on stem cell-based therapy, focusing on its immunomodulatory effects on the pathogenesis of atherosclerosis and how endothelial cells, smooth muscle cells, and other immune cells are regulated by MSCbased therapy.

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Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr−/− mice

Cited by 55 publications

References 40 publications

The Effect of Conditioned Media of Stem Cells Derived from Lipoma and Adipose Tissue on Macrophages’ Response and Wound Healing in Indirect Co-culture System In Vitro

The Effect of Conditioned Media of Stem Cells Derived from Lipoma and Adipose Tissue on Macrophages’ Response and Wound Healing in Indirect Co-culture System In Vitro

The crosstalk: exosomes and lipid metabolism

The involving progress of MSCs based therapy in atherosclerosis

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