Immunomodulatory Properties of Human Adipose Mesenchymal Stromal/Stem Cell in Type 2 Diabetes Milieu. | ||||
| Azhar International Journal of Pharmaceutical and Medical Sciences | ||||
| Article 14, Volume 3, Issue 1, January 2023, Page 144-155 PDF (772.33 K) | ||||
| Document Type: Original research articles | ||||
| DOI: 10.21608/aijpms.2022.150124.1153 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Marwa M Elshahat   1, 2; Nourhan M Abu-Shahba 1, 2; Ghada M Nour El-Din3, 4; Raghda M Ghorab5; Alaa M El-Erian6; Khalda S Amr 2; Osama M Azmy 3, 7, 8; Abeer Ibrahim Abd El-Fattah9
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| 1Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt. | ||||
| 2Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt | ||||
| 3Stem Cell Research Group, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt | ||||
| 4Department of Molecular Genetics and Enzymology, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt | ||||
| 5Department of Immunogenetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt | ||||
| 6Department of Endocrine Surgery, National Institute of Diabetes and Endocrinology, Cairo, Egypt | ||||
| 7Department of Reproductive Health Research, Medical Research Division, National Research Centre, Cairo, Egypt | ||||
| 8Egypt Center for Research and Regenerative Medicine, Cairo, Egypt | ||||
| 9Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt | ||||
| Abstract | ||||
| Adipose tissue is a readily available and plentiful source of multipotent mesenchymal stromal/stem cells (AT-MSC). The immunomodulatory properties of AT-MSC are being introduced in type 2 diabetes (T2D) cell- based therapy. The study aimed to uncover the impact of T2D, on the interplay between AT-MSC and immune cells to develop an effective and safe AT-MSC immunotherapeutic modality. Thus, a direct allogenic co-culture of healthy AT-MSC (nAT-MSC) and peripheral blood mononuclear cells (PBMC), from healthy (nPBMC) or T2D (dPBMC) donors, and stimulated with anti-CD3/CD28, was established in vitro. PBMC proliferation was evaluated by measuring 5-bromo-20-deoxyuridine (Brdu) incorporation in the DNA of proliferating cells in a colorimetric ELISA assay. CD3+ T cell activation surface markers (CD25 and HLA-DR) expression was detected using a flow cytometer. As well, the anti-proliferative effect of naïve and interferon gamma (IFN-ɤ) - primed AT-MSC, isolated from T2D patients (dAT-MSC), on autologous PBMC was explored using the Brdu proliferation assay. In the applied co-culture setting, we observed that the diabetic milieu did not significantly impact the potential of nAT-MSC to suppress stimulated PBMC proliferation. However, it significantly compromised nAT-MSC ability to modulate the activation markers expression, making them less potent to suppress CD25 and HLA-DR expression. Moreover, the dAT-MSC had attenuated ability to suppress the proliferation of autologous stimulated dPBMC, nevertheless, priming of dAT-MSC with IFN-ɤ, could, to an extent, improve such defect. The results suggest that T2D might affect the immunosuppressive potential of AT-MSC and pre-conditioning of dAT-MSC with a pro-inflammatory stimuli could enhance their therapeutic effect. | ||||
| Keywords | ||||
| Type 2 diabetes; Adipose; Mesenchymal; Anti-proliferative; PBMC | ||||
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