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
2009 ◽  
Vol 390 (3) ◽  
pp. 931-936 ◽  
Author(s):  
Jie Liu ◽  
Jian Huang ◽  
Tianxin Lin ◽  
Caixia Zhang ◽  
Xinbao Yin

2020 ◽  
Author(s):  
Tim Tian Y. Han ◽  
Lauren E. Flynn

AbstractAdipose tissue engineering holds promise to address the unmet need in plastic and reconstructive surgery for strategies that promote the stable and predictable regeneration of adipose tissue for volume augmentation applications. Previous studies have demonstrated that decellularized adipose tissue (DAT) scaffolds can provide a pro-adipogenic microenvironment, and that seeding with adipose-derived stromal cells (ASCs) can enhance in vivo angiogenesis and adipogenesis within DAT implants. Recognizing that bioreactor systems can promote cell expansion and infiltration on tissue-engineered scaffolds, this study evaluated the effects of culturing human ASCs on DAT scaffolds within a perfusion bioreactor. Using this system, the impact of both shear stress stimulation and hypoxic preconditioning were explored in vitro and in vivo. Initial studies compared the effects of 14 days of culture within the perfusion bioreactor under 2% O2 or ~20% O2 on human ASC expansion and hypoxia inducible factor 1 alpha (HIF-1α) expression in vitro relative to static cultured controls. The findings indicated that culturing within the bioreactor under 2% O2 significantly increased ASC proliferation on the DAT, with a higher cell density observed in the scaffold periphery. HIF-1α expression was significantly higher when the scaffolds were cultured under 2% O2. Subsequent characterization in a subcutaneous implant model in athymic nude mice revealed that in vivo angiogenesis and adipogenesis were markedly enhanced when the ASCs were cultured on the DAT within the perfusion bioreactor under 2% O2 for 14 days prior to implantation relative to the other culture conditions, as well as additional freshly-seeded and unseeded DAT control groups. Overall, dynamic culture within the perfusion bioreactor system under hypoxia represents a promising approach for preconditioning ASCs on DAT scaffolds to enhance their capacity to stimulate blood vessel formation and infiltration, as well as host-derived adipose tissue regeneration.


Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2419
Author(s):  
Adriana Torres Crigna ◽  
Stefanie Uhlig ◽  
Susanne Elvers-Hornung ◽  
Harald Klüter ◽  
Karen Bieback

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.


2008 ◽  
Vol 599 (1-3) ◽  
pp. 24-31 ◽  
Author(s):  
Han Wang ◽  
Tian-Qing Liu ◽  
Shui Guan ◽  
Yan-Xia Zhu ◽  
Zhan-Feng Cui

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1378
Author(s):  
Peyton Gibler ◽  
Jeffrey Gimble ◽  
Katie Hamel ◽  
Emma Rogers ◽  
Michael Henderson ◽  
...  

Human adipose-derived stromal/stem cells (hASC) are widely used for in vitro modeling of physiologically relevant human adipose tissue. These models are useful for the development of tissue constructs for soft tissue regeneration and 3-dimensional (3D) microphysiological systems (MPS) for drug discovery. In this systematic review, we report on the current state of hASC culture and assessment methods for adipose tissue engineering using 3D MPS. Our search efforts resulted in the identification of 184 independent records, of which 27 were determined to be most relevant to the goals of the present review. Our results demonstrate a lack of consensus on methods for hASC culture and assessment for the production of physiologically relevant in vitro models of human adipose tissue. Few studies have assessed the impact of different 3D culture conditions on hASC adipogenesis. Additionally, there has been a limited use of assays for characterizing the functionality of adipose tissue in vitro. Results from this study suggest the need for more standardized culture methods and further analysis on in vitro tissue functionality. These will be necessary to validate the utility of 3D MPS as an in vitro model to reduce, refine, and replace in vivo experiments in the drug discovery regulatory process.


2013 ◽  
Vol 41 (8) ◽  
pp. S64
Author(s):  
Antonella Conforti ◽  
Marco Scarsella ◽  
Ezio Giorda ◽  
Simone Biagini ◽  
Nadia Starc ◽  
...  

2018 ◽  
Vol 51 (3) ◽  
pp. 1051-1068 ◽  
Author(s):  
Jèssica Latorre ◽  
José M. Moreno-Navarrete ◽  
Mónica Sabater ◽  
Maria Buxo ◽  
José I. Rodriguez-Hermosa ◽  
...  

Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.


Author(s):  
Michael Ghosh ◽  
Hanna Hartmann ◽  
Meike Jakobi ◽  
Léo März ◽  
Leon Bichmann ◽  
...  

Biomaterials play an increasing role in clinical applications and regenerative medicine. A perfectly designed biomaterial should restore the function of damaged tissue without triggering an undesirable immune response, initiate self-regeneration of the surrounding tissue and gradually degrade after implantation. The immune system is well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To obtain a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluated for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these cellular changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials on the immunopeptidome of the monocytic THP-1 cell line. The tested materials included stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulfate. The incubation with all material types resulted in significantly modulated peptides in the immunopeptidome, which were material-associated. The magnitude of induced changes in the immunopeptidome after the stimulation appeared comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation, and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum, whereas HLA class II peptides were mainly induced by stainless steel. These findings provide the first insights into the effects of biomaterials on the immunopeptidome. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. Such efforts will provide a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.


2015 ◽  
Vol 33 (6) ◽  
pp. 385-392 ◽  
Author(s):  
Elena Andreeva ◽  
Irina Andrianova ◽  
Julia Rylova ◽  
Aleksandra Gornostaeva ◽  
Polina Bobyleva ◽  
...  

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