University of Oulu

Marwa Mahmoud and others, Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells, Stem Cells, Volume 41, Issue 5, May 2023, Pages 505–519,

Immunomodulatory functions of adipose mesenchymal stromal/stem cell derived from donors with type 2 diabetes and obesity on CD4 T cells

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Author: Mahmoud, Marwa1,2,3; Juntunen, Miia1,4; Adnan, Amna1,4;
Organizations: 1Adult Stem Cell Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
2Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt
3Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
4Research, Development, and Innovation Centre, Tampere University Hospital, Tampere, Finland
5Biodiversity Interventions for Well-being, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
6Cytokine Biology Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
7Northern Finland Laboratory Centre (NordLab), Oulu, Finland
8Research Unit of Biomedicine, University of Oulu, Oulu, Finland
9Fimlab Laboratories, Tampere, Finland
10Department of Plastic and Reconstructive Surgery, Tampere University Hospital, Tampere, Finland
11Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
12Faculty of Social Sciences, University of Tampere, Tampere, Finland
13Department of Biochemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
14Department of Endocrine Surgery, National Institute of Diabetes and Endocrinology, Cairo, Egypt
15Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland
16Finnish Red Cross Blood Service, Advanced Cell Therapy Centre, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 13.8 MB)
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Language: English
Published: Oxford University Press, 2023
Publish Date: 2023-09-06


For adipose stromal/stem cell (ASCs)-based immunomodulatory therapies, it is important to study how donor characteristics, such as obesity and type 2 diabetes (T2D), influence ASCs efficacy. Here, ASCs were obtained from 2 groups, donors with T2D and obesity (dASCs) or nondiabetic donors with normal-weight (ndASCs), and then cultured with anti-CD3/CD28-stimulated allogeneic CD4 T cells. ASCs were studied for the expression of the immunomodulators CD54, CD274, and indoleamine 2, 3 dioxygenase 1 (IDO) in inflammatory conditions. CD4 T cells cultured alone or in cocultures were assessed to evaluate proliferation, activation marker surface expression, apoptosis, the regulatory T cells (Tregs; CD4⁺ CD25high FOXP3⁺) frequency, and intracellular cytokine expression using flow cytometry. Modulation of T-cell subset cytokines was explored via ELISA. In inflammatory conditions, the expression of CD54, CD274, and IDO was significantly upregulated in ASCs, with no significant differences between ndASCs and dASCs. dASCs retained the potential to significantly suppress CD4 T-cell proliferation, with a slightly weaker inhibitory effect than ndASCs, which was associated with significantly reduced abilities to decrease IL-2 production and increase IL-8 levels in cocultures. Such attenuated potentials were significantly correlated with increasing body mass index. dASCs and ndASCs comparably reduced CD4 T-cell viability, HLA-DR expression, and interferon-gamma production and conversely increased CD69 expression, the Tregs percentage, and IL-17A production. Considerable amounts of the immunomodulators prostaglandin E2 (PGE2) and IL-6 were detected in the conditioned medium of cocultures. These findings suggest that ASCs obtained from donors with T2D and obesity are receptive to the inflammatory environment and able to modulate CD4 T cells accordingly.

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Series: Stem cells
ISSN: 1066-5099
ISSN-E: 1549-4918
ISSN-L: 1066-5099
Volume: 41
Issue: 5
Pages: 505 - 519
DOI: 10.1093/stmcls/sxad021
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the Academy of Finland (decisions 336666, 326588, 312413, 353177, and 31184 for SM and 25013080481 and 25013142041 IJ), the Finnish National Agency for Education, the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital (S.M.). The Competitive State Research Financing of the Expert Responsibility Area of Fimlab Laboratories (grant: X51409 for I.J.), Tampere University Hospital Support Foundation (grant: MK247 (I.J.), Tampere Tuberculosis Foundation (I.J.) and Nordlab Laboratories (grant: X3710-KT0011 for I.J.), Finnish Cultural Foundation (M.J., M.P.) and the Tampere University Doctoral Programme in Medicine, Biosciences and Biomedical Engineering (M.J.).
Copyright information: © The Author(s) 2023. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.