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      Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

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          Abstract

          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.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12015-023-10654-7.

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          Mesenchymal stem cells: immune evasive, not immune privileged.

          James Ankrum, Joon Faii Ong, Jeffrey M Karp (2014)
          The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or 'immune privileged'; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief 'hit and run' mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens.
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            Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications.

            Ying Wang, Xiaodong Chen, Wei Cao … (2014)
            Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in many tissues and are capable of differentiating into several different cell types. Exogenously administered MSCs migrate to damaged tissue sites, where they participate in tissue repair. Their communication with the inflammatory microenvironment is an essential part of this process. In recent years, much has been learned about the cellular and molecular mechanisms of the interaction between MSCs and various participants in inflammation. Depending on their type and intensity, inflammatory stimuli confer on MSCs the ability to suppress the immune response in some cases or to enhance it in others. Here we review the current findings on the immunoregulatory plasticity of MSCs in disease pathogenesis and therapy.
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              Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT).

              Philippe Bourin, Bruce A. Bunnell, Louis Casteilla … (2013)
              Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However, a characterization of the population of adipose-derived stromal and stem cells (ASCs) with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeutics and International Society for Cellular Therapy, this paper sets out to establish minimal definitions of stromal cells both as uncultured stromal vascular fraction (SVF) and as an adherent stromal/stem cells population. Phenotypic and functional criteria for the identification of adipose-derived cells were drawn from the literature. In the SVF, cells are identified phenotypically by the following markers: CD45-CD235a-CD31-CD34+. Added value may be provided by both a viability marker and the following surface antigens: CD13, CD73, CD90 and CD105. The fibroblastoid colony-forming unit assay permits the evaluation of progenitor frequency in the SVF population. In culture, ASCs retain markers in common with other mesenchymal stromal/stem cells (MSCs), including CD90, CD73, CD105, and CD44 and remain negative for CD45 and CD31. They can be distinguished from bone-marrow-derived MSCs by their positivity for CD36 and negativity for CD106. The CFU-F assay is recommended to calculate population doublings capacity of ASCs. The adipocytic, chondroblastic and osteoblastic differentiation assays serve to complete the cell identification and potency assessment in conjunction with a quantitative evaluation of the differentiation either biochemically or by reverse transcription polymerase chain reaction. The goal of this paper is to provide initial guidance for the scientific community working with adipose-derived cells and to facilitate development of international standards based on reproducible parameters. Copyright © 2013 International Society for Cellular Therapy. All rights reserved.
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                Author and article information

                Contributors
                Marwa Mahmoud:
                ORCID: http://orcid.org/0000-0003-2954-4573
                marwa_aromatic_85@yahoo.com
                Journal
                Journal ID (nlm-ta): Stem Cell Rev Rep
                Journal ID (iso-abbrev): Stem Cell Rev Rep
                Title: Stem Cell Reviews and Reports
                Publisher: Springer US (New York )
                ISSN (Print): 2629-3269
                ISSN (Electronic): 2629-3277
                Publication date (Electronic): 14 November 2023
                Publication date PMC-release: 14 November 2023
                Publication date (Print): 2024
                Volume: 20
                Issue: 1
                Pages: 175-205
                Affiliations
                [1 ]Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, ( https://ror.org/02n85j827) 33 El Buhouth St, Ad Doqi, Dokki, 12622 Cairo Governorate Egypt
                [2 ]Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, ( https://ror.org/02n85j827) Cairo, Egypt
                [3 ]Department of Reproductive Health Research, National Research Centre, ( https://ror.org/02n85j827) Cairo, Egypt
                [4 ]Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, ( https://ror.org/05fnp1145) Cairo, Egypt
                Author information
                http://orcid.org/0000-0003-2954-4573
                Article
                Publisher ID: 10654
                DOI: 10.1007/s12015-023-10654-7
                PMC ID: 10799834
                PubMed ID: 37962697
                SO-VID: 62f225d6-cdc3-4147-b5d6-6ac96eea7689
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date accepted : 6 November 2023
                Funding
                Funded by: National Research Centre Egypt
                Open Access :

                Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media, LLC, part of Springer Nature 2024

                Keywords: human adipose stem/stromal cells,immune cells,coculture,immunomodulation,preconditioning,experimental determinants
                Data availability:
                Keywords: human adipose stem/stromal cells, immune cells, coculture, immunomodulation, preconditioning, experimental determinants

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