scholarly journals Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2645
Author(s):  
Assia Eljaafari ◽  
Julien Pestel ◽  
Brigitte Le Magueresse-Battistoni ◽  
Stephanie Chanon ◽  
Julia Watson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
White Adipose Tissue ◽  
Mononuclear Cells ◽  
Cytolytic Activity ◽  
Cell Dysfunction ◽  
T Cell Dysfunction ◽  
The Impact

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.

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

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.

scholarly journals Bone marrow mononuclear cells versus mesenchymal stem cells from adipose tissue on bone healing in an Old World primate: can this be extrapolated to humans?

2019 ◽  
Vol 71 (3) ◽  
pp. 917-928
Author(s):  
E. Branco ◽  
C.M.F.C. Miranda ◽  
A.R. Lima ◽  
K.S.M. Silva ◽  
R.M. Cabral ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Iliac Crest ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Old World ◽  
Bone Injury ◽  
The Right

ABSTRACT In veterinary medicine, the cell therapy is still unexplored and there are many unanswered questions that researchers tend to extrapolate to humans in an attempt to treat certain injuries. Investigating this subject in nonhuman primates turns out to be an unparalleled opportunity to better understand the dynamics of stem cells against some diseases. Thus, we aimed to compare the efficiency of bone marrow mononuclear cells (BMMCs) and mesenchymal stem cells (MSCs) from adipose tissue of Chlorocebus aethiops in induced bone injury. Ten animals were used, male adults subjected, to bone injury the iliac crests. The MSCs were isolated by and cultured. In an autologous manner, the BMMCs were infused in the right iliac crest, and MSCs from adipose tissue in the left iliac crest. After 4.8 months, the right iliac crests fully reconstructed, while left iliac crest continued to have obvious bone defects for up to 5.8 months after cell infusion. The best option for treatment of injuries with bone tissue loss in old world primates is to use autologous MSCs from adipose tissue, suggesting we can extrapolate the results to humans, since there is phylogenetic proximity between species.

Human Adipose Tissue-Derived Mesenchymal Stem Cells Induce Explosive T-Cell Proliferation

2010 ◽  
Vol 19 (12) ◽  
pp. 1843-1853 ◽  
Author(s):  
Meindert J. Crop ◽  
Carla C. Baan ◽  
Sander S. Korevaar ◽  
Jan N.M. Ijzermans ◽  
Willem Weimar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Human Adipose Tissue ◽  
T Cell Proliferation

scholarly journals Mesenchymal Stem Cells Induce Regulatory T-cell Population in Human SLE

2020 ◽  
Vol 19 (4) ◽  
pp. 743-748
Author(s):  
Riyadh Ikhsan ◽  
Agung Putra ◽  
Delfitri Munir ◽  
Dewi Masyithah Darlan ◽  
Bantar Suntoko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Medical Science ◽  
Cell Subset ◽  
Cell Phenotype ◽  
Control Group ◽  
Trypan Blue Exclusion

Background: The mechanisms underlying peripheral disorders during systemic lupus erythematosus (SLE) were found to be shared with tolerance disorders and mediated by T-regulator (T-reg) cells. Mesenchymal stem cells (MSCs) may inhibit T-cell subset differentiation and induce the T-reg cell phenotype. However, the capacity of MSCs to promote functional T-reg cells in SLE patients remains unclear. Objectives: This study aimed to analyze the capacity of MSCs to induce the production of functional CD4+ CD25+ Foxp3+ T-reg cells, in vitro, under co-culture conditions with human SLE cells. Methods: This study used a pre- and post-test control group design. Peripheral blood mononuclear cells (PBMCs) were extracted from SLE patients at the Kariadi Hospital, and MSCs were derived from human umbilical cords (hUCs) The PBMC control group was treated with standard medium, and the treatment group was co-cultured with hUC-MSCs. After 24 hours of co-culture incubation, T-reg cells were removed from the PBMC pool, using magnetic-activated cell sorting (MACS), and the population was assessed using the trypan blue exclusion assay. Results: A significant increase in the population of T-reg cells was observed (P < 0.001) after 24 hours of co-culture incubation with hUC-MSCs. Conclusion: This study concluded that MSCs have the capacity to enhance the T-reg population in human SLE PBMCs. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.743-748

scholarly journals Comparison of Immunological Characteristics of Mesenchymal Stem Cells from the Periodontal Ligament, Umbilical Cord, and Adipose Tissue

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jin-Hee Kim ◽  
Chris H. Jo ◽  
Hang-Rae Kim ◽  
Young-il Hwang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Umbilical Cord ◽  
Periodontal Ligament ◽  
Mononuclear Cells ◽  
Similar Degree ◽  
Minimal Risk ◽  
Peripheral Blood Mononuclear ◽  
Ethical Concerns

Mesenchymal stem cells (MSCs) are of therapeutic importance in the fields of regenerative medicine and immunological diseases. Accordingly, studies evaluating MSCs for clinical applications are increasing. In this study, we characterized MSCs from the periodontal ligament, umbilical cord (UC-MSCs), and adipose tissue, which were relatively easy to obtain with limited ethical concerns regarding their acquisition, and compared their immunological characteristics. Among MSCs isolated from the three different tissues, UC-MSCs grew the fastest in vitro. The three types of MSCs were shown to inhibit proliferation of activated peripheral blood mononuclear cells (PBMCs) to a similar degree, via the indoleamine 2,3-dioxygenase and cyclooxygenase-2 pathways. They were also shown to inhibit the proliferation of PBMCs using HLA-G, which was most prominent in UC-MSCs. Unlike the other two types of MSCs, UC-MSCs showed minimal expression of HLA-DR after activation, suggesting that they pose minimal risk of initiating an allogeneic immune response when administered in vivo. These characteristics, the ease of collection, and the minimal ethical concerns regarding their use suggest UC-MSCs to be suitable MSC therapeutic candidates.

516 Caspase-8 regulated senescence as an immune checkpoint in T lymphocytes for adoptive cell therapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A552-A552
Author(s):  
Valérie Janelle ◽  
Mathieu Neault ◽  
Marie-Eve Lebel ◽  
Dave De Sousa ◽  
Salix Boulet ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cellular Senescence ◽  
Adoptive Cell Therapy ◽  
Great Promise ◽  
Caspase 8 ◽  
Cell Dysfunction ◽  
Human T Cell ◽  
T Cell Dysfunction ◽  
The Impact

BackgroundThe development of immunotherapies holds great promise for the treatment of refractory infections and cancer. Current approaches, although effective in many settings, have limitations that prevent their widespread use. Hence, several aspects require improvements, including the re-wiring of T-cell fates and function. T-cell dysfunction is central to the persistence of several chronic viral infections and the progression of malignancies. Upon activation, T cells can follow several paths of differentiation, leading to terminal effector differentiation and/or exhaustion which are widely recognized as dysfunctional features limiting human immune competence. Furthermore, dysfunctional features induced during laboratory-based manipulations of T-cell products prior to adoptive cell transfer has a determining effect on outcomes. Similarly, repeated antigen encounters after transfer in vivo favors the development of T-cell dysfunction. However, the nature and underlying mechanisms of T-cell dysfunction are still incompletely understood.MethodsCombining genomics, phenotypic and functional analyses in various physiologically and clinically relevant settings, we investigated the key factors leading to T-cell dysfunction. Specifically, we evaluated the impact of repeated stimulations using CD3/CD28-coated beads or antigen-loaded dendritic cells in human T-cell long term cultures, and BCMA-expressing cells for anti-BCMA CAR T cells. We also examined mouse antigen-specific T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection as well as datasets obtained from circulating T cells from acute myeloid leukemia (AML) patients.ResultsWe identified telomere-independent cellular senescence as a central aspect of exhausted PD-1-expressing T cells following repeated stimulations. Mechanistically, it is associated the induction of p16INK4a. Additionally, we found that cellular senescence features are partly regulated by the activation of caspase-8, through a non-apoptotic function of this molecule not previously described in T cells.ConclusionsWe thus conclude that caspase-8 may regulate the balance between apoptosis and proliferation by protecting T cells from cellular senescence. Senescence-associated mechanisms may be seen as key players in T-cell dysfunction occurring following repeated stimulations and as such should be considered as novel immune checkpoints impeding the success of T-cell adoptive immunotherapy in humans.Ethics ApprovalThis study was approved by the local Maisonneuve-Rosemont Hospital research ethics authorities and participants’ informed consent was obtained (CÉR2020-2141 and CÉR13030).

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