Immunomodulatory Properties of Human Adipose Mesenchymal Stromal/Stem Cell in Type 2 Diabetes Milieu.

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. Expression levels of CD3 + T cell activation surface markers (CD25 and HLA-DR) were 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, the diabetic milieu does not significantly impact the potential of nAT-MSC to suppress stimulated PBMC proliferation. However, it significantly compromises nAT-MSC ability to modulate the activation markers expression, making them less potent to suppress CD25 and HLA-DR expression. Moreover, the dAT-MSC have attenuated ability to suppress the proliferation of autologous stimulated dPBMC, nevertheless, priming of dAT-MSC with IFN-ɤ, might 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 stimulus could enhance their therapeutic effect.

Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

“…Such results suggest a possible weaker control of T cell activation by autologous ASCs of RD patients in vivo [ 47 ]. In the context of diabetes mellitus, hASCs, from patients with type 2 diabetes (T2D), exhibited compromised antiproliferative potential on autologous anti-CD3/CD28-activated peripheral blood mononuclear cells (PBMCs) [ 48 ]. However, co-transplantation of autologous ASC-derived insulin-producing cells and hematopoietic stem cells showed a better response in individuals with type 1 diabetes (T1D) as compared with a similar allogeneic regimen [ 49 ].…”