scholarly journals Adipose-Derived Stem Cells from Obese Donors Polarize Macrophages and Microglia toward a Pro-Inflammatory Phenotype

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 26
Author(s):  
Mark A. A. Harrison ◽  
Rachel M. Wise ◽  
Brooke P. Benjamin ◽  
Emily M. Hochreiner ◽  
Omair A. Mohiuddin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Potential ◽  
Disease States ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
And Migration ◽  
Inflammatory Phenotypes ◽  
Donor Characteristics ◽  
The Impact ◽  
Individual Donor

Macrophages and microglia represent the primary phagocytes and first line of defense in the peripheral and central immune systems. They activate and polarize into a spectrum of pro- and anti-inflammatory phenotypes in response to various stimuli. This activation is tightly regulated to balance the appropriate immune response with tissue repair and homeostasis. Disruption of this balance results in inflammatory disease states and tissue damage. Adipose stem cells (ASCs) have great therapeutic potential because of the potent immunomodulatory capabilities which induce the polarization of microglia and macrophages to the anti-inflammatory, M2, phenotype. In this study, we examined the effects of donor heterogeneity on ASC function. Specifically, we investigated the impact of donor obesity on ASC stemness and immunomodulatory abilities. Our findings revealed that ASCs from obese donors (ObASCs) exhibited reduced stem cell characteristics when compared to ASCs from lean donors (LnASCs). We also found that ObASCs promote a pro-inflammatory phenotype in murine macrophage and microglial cells, as indicated by the upregulated expression of pro-inflammatory genes, increased nitric oxide pathway activity, and impaired phagocytosis and migration. These findings highlight the importance of considering individual donor characteristics such as obesity when selecting donors and cells for use in ASC therapeutic applications and regenerative medicine.

scholarly journals Comparative Phenotypic and Functional Analyses of the Effects of IL-10 or TGF-β on Porcine Macrophages

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1098
Author(s):  
Tania Carta ◽  
Elisabetta Razzuoli ◽  
Floriana Fruscione ◽  
Susanna Zinellu ◽  
Dionigia Meloni ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Phagocytic Cells ◽  
Mhc Ii ◽  
Tnf Α ◽  
Regulated Expression ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Functional Analyses ◽  
The Impact ◽  
Immunosuppressive Cytokines

Macrophages are phagocytic cells involved in maintaining tissue homeostasis and defense against pathogens. Macrophages may be polarized into different functionally specialized subsets. M2c macrophages arise following stimulation with IL-10 or TGF-β and mediate anti-inflammatory and tissue repair functions. M2c macrophages remain poorly characterized in the pig, thus we investigated the impact of these regulatory cytokines on porcine monocyte-derived macrophages (moMΦ). The phenotype and functionality of these cells was characterized though confocal microscopy, flow cytometry, ELISA, and RT-qPCR. Both cytokines induced CD14 and MHC II DR down-regulation and reduced IL-6, TNF-α, and CD14 expression, suggestive of an anti-inflammatory phenotype. Interestingly, neither IL-10 or TGF-β were able to trigger IL-10 induction or release by moMΦ. Differences between these cytokines were observed: stimulation with IL-10, but not TGF-β, induced up-regulation of both CD16 and CD163 on moMΦ. In addition, IL-10 down-regulated expression of IL-1β and IL-12p40 4h post-stimulation and induced a stronger impairment of moMΦ ability to respond to either TLR2 or TLR4 agonists. Overall, our results provide an overview of porcine macrophage polarization by two immunosuppressive cytokines, revealing differences between IL-10 and TGF-β, and reporting some peculiarity of swine, which should be considered in translational studies.

scholarly journals Differential Effector Response of Amnion- and Adipose-Derived Mesenchymal Stem Cells to Inflammation; Implications for Intradiscal Therapy

2019 ◽  
Author(s):  
Ryan Borem ◽  
Allison Madeline ◽  
Mackenzie Bowman ◽  
Sanjitpal Gill ◽  
John Tokish ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Optimal Choice ◽  
Human Mscs ◽  
Tissue Destruction ◽  
Effector Functions ◽  
Anti Inflammatory ◽  
Factor Α ◽  
The Impact

ABSTRACTIntervertebral disc degeneration (IVDD) is a progressive condition marked by inflammation and tissue destruction. The effector functions of mesenchymal stem cells (MSCs) make them an attractive therapy for patients with IVDD. While several sources of MSCs exist, the optimal choice for use in the inflamed IVD remains a significant question. Adipose (AD)- and amnion (AM)-derived MSCs have several advantages compared to other sources, however, no study has directly compared the impact of IVDD inflammation on their effector functions. Human MSCs were cultured in media with or without supplementation of interleukin-1β and tumor necrosis factor-α at concentrations produced by IVDD cells. MSC proliferation and production of pro- and anti-inflammatory cytokines were quantified following 24- and 48-hours of culture. Additionally, the osteogenic and chondrogenic potential of AD- and AM-MSCs was characterized via histology and biochemical analysis following 28 days of culture. In inflammatory culture, AM-MSCs produced significantly more anti-inflammatory IL-10 (p=0.004) and larger chondrogenic pellets (p=0.04) with greater percent area staining positively for glycosaminoglycan (p<0.001) compared to AD-MSCs. Conversely, AD-MSCs proliferated more resulting in higher cell numbers (p=0.048) and produced higher concentrations of pro-inflammatory cytokines PGE2 (p=0.030) and IL-1β (p=0.010) compared to AM-MSCs. Additionally, AD-MSCs produced more mineralized matrix (p<0.001) compared to AM-MSCs. These findings begin to inform researchers and clinicians as to which MSC source may be optimal for different IVD therapies including those that may promote regeneration or fusion. Further study is warranted evaluating these cells in systems which recapitulate the nutrient- and oxygen-deprived environment of the degenerate IVD.

Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells

2011 ◽  
Vol 35 (3) ◽  
pp. 235-248 ◽  
Author(s):  
Maike Müller ◽  
Oksana Raabe ◽  
Klaus Addicks ◽  
Sabine Wenisch ◽  
Stefan Arnhold
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
And Migration

scholarly journals Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1567
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Dark Phase ◽  
Anti Inflammatory ◽  
The Impact

Melatonin (MLT) is a powerful chronobiotic hormone that controls a multitude of circadian rhythms at several levels and, in recent times, has garnered considerable attention both from academia and industry. In several studies, MLT has been discussed as a potent neuroprotectant, anti-apoptotic, anti-inflammatory, and antioxidative agent with no serious undesired side effects. These characteristics raise hopes that it could be used in humans for central nervous system (CNS)-related disorders. MLT is mainly secreted in the mammalian pineal gland during the dark phase, and it is associated with circadian rhythms. However, the production of MLT is not only restricted to the pineal gland; it also occurs in the retina, Harderian glands, gut, ovary, testes, bone marrow, and lens. Although most studies are limited to investigating the role of MLT in the CNS and related disorders, we explored a considerable amount of the existing literature. The objectives of this comprehensive review were to evaluate the impact of MLT on the CNS from the published literature, specifically to address the biological functions and potential mechanism of action of MLT in the CNS. We document the effectiveness of MLT in various animal models of brain injury and its curative effects in humans. Furthermore, this review discusses the synthesis, biology, function, and role of MLT in brain damage, and as a neuroprotective, antioxidative, anti-inflammatory, and anticancer agent through a collection of experimental evidence. Finally, it focuses on the effect of MLT on several neurological diseases, particularly CNS-related injuries.

scholarly journals Pentraxin-3 Modulates Osteogenic/Odontogenic Differentiation and Migration of Human Dental Pulp Stem Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5778
Author(s):  
Yeon Kim ◽  
Joo-Yeon Park ◽  
Hyun-Joo Park ◽  
Mi-Kyoung Kim ◽  
Yong-Il Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Dental Pulp Stem Cells ◽  
Pentraxin 3 ◽  
Odontogenic Differentiation ◽  
Human Dental Pulp ◽  
And Migration

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.

scholarly journals The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Soukaina Bahsoun ◽  
Karen Coopman ◽  
Elizabeth C. Akam
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
Surface Marker Expression ◽  
Wide Range ◽  
And Migration ◽  
The Impact

AbstractMesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.

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