Comparison of biological properties of human adipose tissue-derived mesenchymal stem/ stromal cells from healthy and diabetic donors: consequences for cell-based medicinal product development.

BACKGROUND: Diabetes mellitus is a civilisation disease that can cause damage to tissues and organs as well as affects the biological properties of cells isolated from these tissues. In recent years, there has been increasing interest in cell-based therapies, including the use of mesenchymal stem/stromal cells (MSCs). Therefore, the aim of the current study was to compare the biological potential of adipose tissue-derived MSCs (AT-MSCs) from healthy and diabetic donors under in vitro conditions and to clarify the implications for cell-based medicinal product development. Biological potential of both populations of AT-MSCs was also investigated in the relation to their major therapeutic mechanisms of action-we focused on the chondrogenic and osteogenic differentiation capacity of AT-MSCs and their pro-angiogenic potential. METHODS: Human AT-MSCs derived from healthy and type 2 diabetes (T2D) donors underwent biological characterization including assessment of: morphology, viability, antigenic profile, proliferation, presence of senescent cells and oxidative stress, pro-angiogenic properties of AT-MSC secretome as well as trilineage differentiation potential in vitro. AT-MSCs were cultured under the control and diabetes mimicking culture conditions. RESULTS: We observed no significant differences in morphology, viability, expression of MSC markers, proliferation rate, concentration of oxidative stress marker (8OHdG) and content of senescent cells between AT-MSCs from healthy and T2D donors under control culture conditions. The conditioned medium from a culture of diabetic AT-MSCs was found to improve the pro-angiogenic potential of human umbilical vein endothelial cells (HUVECs), compared with the medium from healthy AT-MSCs. HUVECs that were incubated in conditioned media collected from healthy AT-MSCs from diabetic culture conditions, exhibited greater potential to form capillary-like structures. Furthermore, diabetic culture conditions induced the oxidative stress in healthy AT-MSCs. Diabetic AT-MSCs exhibited greater chondrogenic differentiation capacity along with lower adipogenic differentiation potential and comparable osteogenic differentiation capacity when compared to healthy donor-derived AT-MSCs. CONCLUSIONS: The present study provides evidence of the biological potential of AT-MSCs from diabetic donors, which can be used as an active substance in the development of cell-based autologous advanced therapy medicinal products (ATMPs) dedicated for the treatment of e.g. osteoarthritis or myocardial infarction. Diabetic AT-MSCs in the used culture conditions are functional cells with greater chondrogenic and pro-angiogenic potential when compared to AT-MSCs from healthy donors. This increases the possibility of treating diabetic patients using their own cells.