scholarly journals Human Adipose Tissue-Derived Stromal Cells Suppress Human, but Not Murine Lymphocyte Proliferation, via Indoleamine 2,3-Dioxygenase Activity

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2419
Author(s):  
Adriana Torres Crigna ◽  
Stefanie Uhlig ◽  
Susanne Elvers-Hornung ◽  
Harald Klüter ◽  
Karen Bieback
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Lymphocyte Proliferation ◽  
Molecular Mechanisms ◽  
Human Adipose Tissue ◽  
Kynurenine Pathway ◽  
Cell Contact ◽  
Indoleamine 2,3 Dioxygenase ◽  
Murine Lymphocyte

Over recent years, mesenchymal stromal cells (MSC) have gained immense attraction in immunotherapy, regenerative medicine and tissue engineering. MSC microenvironment modulation occurs through synergy of direct cell–cell contact, and secreted soluble factors and extracellular vesicles (EV). MSC-derived EV have been suggested as cell-free immunomodulatory alternative to MSC; however, previous findings have challenged this. Furthermore, recent data suggest that evaluating the mechanism of action of human MSC (hMSC) in animal models might promote adverse immune reactions or lack of functionality due to xeno-incompatibilities. In this study, we first assessed the immunomodulatory strength of different human MSC sources on in vitro stimulated T cells and compared this to interferon-gamma (IFNγ) primed MSC conditioned medium (CM) and EV. Second, we addressed the main molecular mechanisms, and third, we assessed the MSC in vitro immunosuppressive effect across interspecies barriers. We identified human adipose tissue-derived stromal cells (ASC) with strongest immunomodulatory strength, followed by bone marrow (BM) and cord blood-derived MSC (CB). Whilst CM from primed ASC managed to exert analogous effects as their cellular counterpart, EV derived thereof did not, reproducing previous findings. IFNγ-induced indoleamine 2,3-dioxygenase (IDO) activity was identified as key mechanism to suppress human lymphocyte proliferation, as in the presence of the IDO inhibitor epacadostat (Epac) a stimulation of proliferation was seen. In addition, we revealed MSC immunosuppressive effects to be species-specific, because human cells failed to suppress murine lymphocyte proliferation. In summary, ASC were the strongest immunomodulators with the IDO-kynurenine pathway being key within the human system. Importantly, the in vitro lack of interspecies immunomodulatory strength suggests that preclinical data need to be carefully interpreted especially when considering a possible translation to clinical field.

Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype

2010 ◽  
Vol 42 (12) ◽  
pp. 895-901 ◽  
Author(s):  
Nathalie Saulnier ◽  
Anna Chiara Piscaglia ◽  
Maria Ausiliatrice Puglisi ◽  
Marta Barba ◽  
Vincenzo Arena ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Human Adipose Tissue

scholarly journals Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 334
Author(s):  
Aisha Y. Madani ◽  
Yasser Majeed ◽  
Houari B. Abdesselem ◽  
Maha V. Agha ◽  
Muneera Vakayil ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Adenosine Monophosphate ◽  
Human Adipose Tissue ◽  
Premature Aging ◽  
Guanosine Monophosphate ◽  
Negative Regulator ◽  
Signal Transducer ◽  
Interferon Signaling

Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Here, we describe a robust and physiologically relevant in vitro system to trigger senescence in mouse 3T3-L1 preadipocytes. By employing transcriptomics analyses, we discovered up-regulation of key pro-inflammatory molecules and activation of interferon/signal transducer and activator of transcription (STAT)1/3 signaling in senescent preadipocytes, and expression of downstream targets was induced in epididymal WAT of obese mice, and obese human adipose tissue. To test the relevance of STAT1/3 signaling to preadipocyte senescence, we used Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology to delete STAT1/3 and discovered that STAT1 promoted growth arrest and cooperated with cyclic Guanosine Monophosphate-Adenosine Monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) to drive the expression of interferon β (IFNβ), C-X-C motif chemokine ligand 10 (CXCL10), and interferon signaling-related genes. In contrast, we discovered that STAT3 was a negative regulator of STAT1/cGAS-STING signaling—it suppressed senescence and inflammation. These data provide insights into how STAT1/STAT3 signaling coordinates senescence and inflammation through functional interactions with the cGAS/STING pathway.

In vitro differentiation of neural cells from human adipose tissue derived stromal cells

2018 ◽  
Vol 66 (3) ◽  
pp. 716 ◽  
Author(s):  
ShrutiD Dave ◽  
ChetanN Patel ◽  
ArunaV Vanikar ◽  
HargovindL Trivedi
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Human Adipose Tissue ◽  
Neural Cells ◽  
In Vitro Differentiation

scholarly journals Periostin expression and characters of human adipose tissue-derived mesenchymal stromal cells were aberrantly affected by in vitro cultivation

2019 ◽  
Vol 6 ◽  
pp. 33-33 ◽  
Author(s):  
Heba M. Saad Eldien ◽  
Hekmat Osman Abdel-Aziz ◽  
Douaa Sayed ◽  
Wafaa Mubarak ◽  
Hemmat H. G. Hareedy ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Adipose Tissue ◽  
In Vitro Cultivation

scholarly journals Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

2020 ◽  
Vol 21 (3) ◽  
pp. 799 ◽  
Author(s):  
Joanna Lelek ◽  
Ewa K. Zuba-Surma
Keyword(s):  
Adipose Tissue ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Differentiation Potential

Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

scholarly journals Interaction of allogeneic adipose tissue-derived stromal cells and unstimulated immune cells in vitro: the impact of cell-to-cell contact and hypoxia in the local milieu

2017 ◽  
Vol 70 (1) ◽  
pp. 299-312 ◽  
Author(s):  
Aleksandra N. Gornostaeva ◽  
Elena R. Andreeva ◽  
Polina I. Bobyleva ◽  
Ludmila B. Buravkova
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Stromal Cells ◽  
Cell Contact ◽  
The Impact

scholarly journals Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and In Vivo

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6278 ◽  
Author(s):  
Beatrice Cousin ◽  
Emmanuel Ravet ◽  
Sandrine Poglio ◽  
Fabienne De Toni ◽  
Mélanie Bertuzzi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Adipose Tissue ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Pancreatic Cancer Cell ◽  
Human Adipose Tissue ◽  
Cancer Cell Death
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