An analysis of the immunomodulatory properties of human spheroids from adipose-derived stem cells

Toia, Francesca; Elena, Lo Presti; Barbara, Di Stefano Anna; Marta, Di Simone; Trapani, Marco; Maria, Corsale Anna; Carmela, Picone; Francesco, Moschella; Dieli, Francesco; Adriana, Cordova; Serena, Meraviglia

doi:10.1016/j.lfs.2023.121610

Cited by 2 publications

(4 citation statements)

References 28 publications

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“…At the attachment sites, elevated expression of intracellular adhesion molecule 1 (ICAM-1)/CD54 was detected, indicating the formation of highly specific ligand-receptor contacts b/w interacting cells [ 58 ]. Recently, ASC spheroids modulated effectively the proliferation and cytokine production of allogenic γδ CD3 + T lymphocytes in direct contact, while their conditioned medium (CM) induced much weaker inhibitory effects [ 59 ].…”

Section: Coculture Setting Parametersmentioning

confidence: 99%

“…Limited studies addressed the immunomodulatory phenotype and/or functions of scaffold free- 3D ASC spheroids in vitro [ 59 , 86 , 166 ]. hASC aggregates, obtained by the hanging drop technique, exhibited a stronger ability than 2D counterparts, to modulate macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype in vitro, presumably via elevated PGE2 production [ 86 ].…”

Section: Asc-related Parametersmentioning

confidence: 99%

“…hASC aggregates, obtained by the hanging drop technique, exhibited a stronger ability than 2D counterparts, to modulate macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype in vitro, presumably via elevated PGE2 production [ 86 ]. Recently, ASC spheroids significantly abrogated the proliferation and IFN-ɤ secretion and promoted the production of the anti-inflammatory cytokines IL-9 in coculture with stimulated γδ CD3 + T lymphocytes [ 59 ]. γδ CD3 + T lymphocytes represent a bridge b/w innate and adaptive T cell responses and produce high levels of IL-17 in obesity contributing to AT inflammation and insulin resistance [ 77 ].…”

Section: Asc-related Parametersmentioning

confidence: 99%

“…γδ CD3 + T lymphocytes represent a bridge b/w innate and adaptive T cell responses and produce high levels of IL-17 in obesity contributing to AT inflammation and insulin resistance [ 77 ]. The detected anti-inflammatory effects were greater than those observed by adherent ASCs due to higher levels of the immunomodulators IL-5, IL-10, IL-4 and IL-13 in the ASC spheroid secretome [ 59 ]. In another report, comparative gene expression analysis in 2D vs. 3D (in ultra-low attachment surfaces) ASC cultures revealed superior expression, of genes involved in stemness ( SOX2, POU5F1, and NANOG ), anti-aging ( SIRT1 ), and anti-inflammation ( TGF-β1 ), however, lower expression of those involved in oxidative stress ( ALDH3 ), in 3D ASC spheres [ 166 ].…”

Section: Asc-related Parametersmentioning

confidence: 99%

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Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

Mahmoud,

Abdel-Rasheed,

Galal

et al. 2023

Stem Cell Rev and Rep

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Human adipose tissue-derived stem/stromal cells (hASCs) are adult multipotent mesenchymal stem/stromal cells with immunomodulatory capacities. Here, we present up-to-date knowledge on the impact of different experimental and donor-related factors on hASC immunoregulatory functions in vitro. The experimental determinants include the immunological status of hASCs relative to target immune cells, contact vs. contactless interaction, and oxygen tension. Factors such as the ratio of hASCs to immune cells, the cellular context, the immune cell activation status, and coculture duration are also discussed. Conditioning of hASCs with different approaches before interaction with immune cells, hASC culture in xenogenic or xenofree culture medium, hASC culture in two-dimension vs. three-dimension with biomaterials, and the hASC passage number are among the experimental parameters that greatly may impact the hASC immunosuppressive potential in vitro, thus, they are also considered. Moreover, the influence of donor-related characteristics such as age, sex, and health status on hASC immunomodulation in vitro is reviewed. By analysis of the literature studies, most of the indicated determinants have been investigated in broad non-standardized ranges, so the results are not univocal. Clear conclusions cannot be drawn for the fine-tuned scenarios of many important factors to set a standard hASC immunopotency assay. Such variability needs to be carefully considered in further standardized research. Importantly, field experts’ opinions may help to make it clearer. Graphical Abstract Parameters that promote ASC immunosuppression on immune cells. Activation of immune cells induces their proliferation and differentiation and presence of ASCs modulates/suppresses such consequences. Augmented immunosuppressive effects of ASCs can be introduced in direct contact with the immune cells and via complementing the repeatedly reported experimental settings (texts in grey shapes). Abbreviations: ASCs: adipose tissue-derived stem/stromal cells, IFN-ɤ: Interferon gamma, MLR: Mixed lymphocyte reaction, TNF: Tumor necrosis factor.

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Section: Coculture Setting Parametersmentioning

confidence: 99%

Section: Asc-related Parametersmentioning

confidence: 99%

Section: Asc-related Parametersmentioning

confidence: 99%

Section: Asc-related Parametersmentioning

confidence: 99%

See 2 more Smart Citations

Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

Mahmoud,

Abdel-Rasheed,

Galal

et al. 2023

Stem Cell Rev and Rep

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Characterization of the Secretome from Spheroids of Adipose-Derived Stem Cells (SASCs) and Its Potential for Tissue Regeneration

Urrata,

Toia,

Cammarata

et al. 2024

Biomedicines

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Introduction: Spheroids are spherical aggregates of cells that mimic the three-dimensional (3D) architecture of tissues more closely than traditional two dimensional (2D) cultures. Spheroids of adipose stem cells (SASCs) show special features such as high multilineage differentiation potential and immunomodulatory activity. These properties have been attributed to their secreted factors, such as cytokines and growth factors. Moreover, a key role is played by the extracellular vesicles (EVs), which lead a heterogeneous cargo of proteins, mRNAs, and small RNAs that interfere with the pathways of the recipient cells. Purpose: The aim of this work was to characterize the composition of the secretome and exosome from SASCs and evaluate their regenerative potential. Materials and Methods: SASCs were extracted from adipose samples of healthy individuals after signing informed consent. The exosomes were isolated and characterized by Dinamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Western blotting analyses. The expression of mRNAs and miRNAs were evaluated through real-time PCR. Lastly, a wound-healing assay was performed to investigate their regenerative potential on different cell cultures. Results: The SASCs’ exosomes showed an up-regulation of NANOG and SOX2 mRNAs, typical of stemness maintenance, as well as miR126 and miR146a, related to angiogenic and osteogenic processes. Moreover, the exosomes showed a regenerative effect. Conclusions: The SASCs’ secretome carried paracrine signals involved in stemness maintenance, pro-angiogenic and pro-osteogenic differentiation, immune system regulation, and regeneration.

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An analysis of the immunomodulatory properties of human spheroids from adipose-derived stem cells

Cited by 2 publications

References 28 publications

Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

Characterization of the Secretome from Spheroids of Adipose-Derived Stem Cells (SASCs) and Its Potential for Tissue Regeneration

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