Exosomes From Adipose-Derived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue

The application of liposuctioned white adipose tissue (L-WAT) and adipose-derived stem cells (ADSCs) as a novel immunomodulatory treatment option is the currently subject of various clinical trials. Because it is crucial to understand the underlying therapeutic mechanisms, the latest studies focused on the immunomodulatory functions of L-WAT or ADSCs. However, studies that examine the specific transcriptional adaptation of these treatment options to an extrinsic inflammatory stimulus in an unbiased manner are scarce. The aim of this study was to compare the gene expression profile of L-WAT and ADSCs, when subjected to tumor necrosis factor alpha (TNFα), and to identify key factors that might be therapeutically relevant when using L-WAT or ADSCs as an immuno-modulator. Fat tissue was harvested by liposuction from five human donors. ADSCs were isolated from the same donors and shortly subjected to expansion culture. L-WAT and ADSCs were treated with human recombinant TNFα, to trigger a strong inflammatory response. Subsequently, an mRNA deep next-generation sequencing was performed to evaluate the different inflammatory responses of L-WAT and ADSCs. We found significant gene expression changes in both experimental groups after TNFα incubation. However, ADSCs showed a more homogenous gene expression profile by predominantly expressing genes involved in immunomodulatory processes such as CCL19, CCL5, TNFSF15 and IL1b when compared to L-WAT, which reacted rather heterogeneously. As RNA sequencing between L-WAT and ADSCS treated with TNFα revealed that L-WAT responded very heterogeneously to TNFα treatment, we therefore conclude that ADSCs are more reliable and predictable when used therapeutically. Our study furthermore yields insight into potential biological processes regarding immune system response, inflammatory response, and cell activation. Our results can help to better understand the different immunomodulatory effects of L-WAT and ADSCs.

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Derivation, characterization, and in vitro cell regeneration of canine white adipose tissue-derived mesenchymal stem cells obtained from a mesenteric region

The Journal of Basic and Applied Zoology ◽

10.1186/s41936-021-00222-1 ◽

2021 ◽

Vol 82 (1) ◽

Author(s):

Anirban Mandal ◽

Ajeet Kumar Jha ◽

Dew Biswas ◽

Shyamal Kanti Guha

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Stromal Vascular Fraction ◽

Cell Regeneration ◽

Wound Healing Assay ◽

Chain Reaction ◽

Polymerase Chain

Abstract Background The study was conducted to assess the characterization, differentiation, and in vitro cell regeneration potential of canine mesenteric white adipose tissue-derived mesenchymal stem cells (AD-MSCs). The tissue was harvested through surgical incision and digested with collagenase to obtain a stromal vascular fraction. Mesenchymal stem cells isolated from the stromal vascular fraction were characterized through flow cytometry and reverse transcription-polymerase chain reaction. Assessment of cell viability, in vitro cell regeneration, and cell senescence were carried out through MTT assay, wound healing assay, and β-galactosidase assay, respectively. To ascertain the trilineage differentiation potential, MSCs were stained with alizarin red for osteocytes, alcian blue for chondrocytes, and oil o red for adipocytes. In addition, differentiated cells were characterized through a reverse transcription-polymerase chain reaction. Results We observed the elongated, spindle-shaped, and fibroblast-like appearance of cells after 72 h of initial culture. Flow cytometry results showed positive expression for CD44, CD90, and negative expression for CD45 surface markers. Population doubling time was found 18–24 h for up to the fourth passage and 30±0.5 h for the fifth passage. A wound-healing assay was used to determine cell migration rate which was found 136.9 ± 4.7 μm/h. We observed long-term in vitro cell proliferation resulted in MSC senescence. Furthermore, we also found that the isolated cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Conclusions Mesenteric white adipose tissue was found to be a potential source for isolation, characterization, and differentiation of MSCs. This study might be helpful for resolving the problems regarding the paucity of information concerning the basic biology of stem cells. The large-scale use of AD-MSCs might be a remedial measure in regenerative medicine.

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The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells

Biomaterials ◽

10.1016/j.biomaterials.2010.02.046 ◽

2010 ◽

Vol 31 (17) ◽

pp. 4715-4724 ◽

Cited By ~ 212

Author(s):

L.E. Flynn

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Adipogenic Differentiation ◽

Adipose Derived Stem Cells

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Adipose tissue engineering with naturally derived scaffolds and adipose-derived stem cells

Biomaterials ◽

10.1016/j.biomaterials.2007.05.002 ◽

2007 ◽

Vol 28 (26) ◽

pp. 3834-3842 ◽

Cited By ~ 107

Author(s):

Lauren Flynn ◽

Glenn D. Prestwich ◽

John L. Semple ◽

Kimberly A. Woodhouse

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Adipose Tissue ◽

Adipose Derived Stem Cells ◽

Adipose Tissue Engineering

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Isolation, Culture, and Adipogenic Induction of Neural Crest Original Adipose-Derived Stem Cells from Periaortic Adipose Tissue

Journal of Visualized Experiments ◽

10.3791/60691 ◽

2020 ◽

Author(s):

Yiding Qi ◽

Xiang Miao ◽

Lian Xu ◽

Mengxia Fu ◽

Shi Peng ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Neural Crest ◽

Adipose Derived Stem Cells

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Assessment of human cartilage regeneration in a patient with knee osteoarthritis using autologous adipose-tissue-derived stem cells and Platelet-rich plasma: a case study

Journal of Surgery and Trauma ◽

10.32592/jsurgery.2020.8.2.104 ◽

2020 ◽

pp. 73-78

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Physical Therapy ◽

Platelet Rich Plasma ◽

Cartilage Regeneration ◽

Adipose Derived Stem Cells ◽

Human Cartilage ◽

Percutaneous Injection ◽

Knee Oa ◽

Mri Scans

Cartilage regenerative medicine has been met with much interest due to their ability to inhibit disease progression of osteoarthritis (OA). The use of adipose-derived stem cells has been suggested as a reliable method for OA treatment because of their potential to differentiate into a variety of cell lines and their potent capability to self-renewal and repair. The aim of this study is to assess adipose-derived stem cells in combination with PRP ability in treating a patient with knee OA. A 53-year- old man with osteoarthritis was selected for this treatment. Human abdominal subcutaneous adipose sample was obtained from a patient with knee OA. Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. ADSCs cultured in DMEM medium supplemented with 10% FBS. Also, ADSCs expanded and characterized by flow cytometry. These stem cells, along with platelet-rich plasma and calcium chloride, were injected into the right knee. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. The MRI data for the patient demonstrated significant positive changes. Probable cartilage regeneration was sensible in the patient. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous adipose-derived stem cell injection, in conjunction with platelet-rich plasma is a promising minimally invasive therapy for osteoarthritis of human knees. The present clinical case report demonstrated that a combination of percutaneous injection of autologous ADSCs and PRPmay be able to regenerate cartilage in human knee OA.

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Aging-related inflammation driven by cellular senescence enhances NAD consumption via activation of CD38+pro-inflammatory macrophages

10.1101/609438 ◽

2019 ◽

Cited By ~ 7

Author(s):

Anthony J. Covarrubias ◽

Abhijit Kale ◽

Rosalba Perrone ◽

Jose Alberto Lopez-Dominguez ◽

Angela Oliveira Pisco ◽

...

Keyword(s):

Adipose Tissue ◽

Inflammatory Cytokines ◽

Cellular Senescence ◽

White Adipose Tissue ◽

Causal Link ◽

Secretory Proteins ◽

M2 Macrophages ◽

Therapeutic Opportunity ◽

Inflammatory Macrophages ◽

Novel Therapeutic

SummaryDecline in tissue NAD levels during aging is linked to aging and its associated diseases. However, the mechanism for aging-associated NAD decline remains unclear. Here we report that pro-inflammatory M1-like macrophages, but not naïve or M2 macrophages, accumulate in metabolic tissues including visceral white adipose tissue and the liver during aging. Remarkably, these M1-like macrophages highly express the NAD consuming enzyme CD38 and have enhanced CD38-dependent NADase activity. We also find that senescent cells progressively accumulate in visceral white adipose tissue during aging and that inflammatory cytokines found in the supernatant from senescent cells (Senescence associated secretory proteins, SASP) induce macrophages to proliferate and to express CD38. These results highlight a new causal link between visceral tissue senescence and tissue NAD decline during aging and represent a novel therapeutic opportunity targeting maintenance of NAD levels during aging.

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