The role of Insulin Growth Factor axis in stem cell based periodontal regeneration under diabetic conditions

Periodontitis and diabetes mellitus (DM) are two of the most common and challenging health problems worldwide, and they affect each other mutually and adversely. Current periodontal therapies have unpredictable outcome in diabetic patients. Periodontal tissue engineering is a challenging but promising approach that aims at restoring periodontal tissues using one or all of the following: stem cells, signalling molecules and scaffolds. Mesenchymal stem/stromal cells (MSCs) and Insulin-like growth factor (IGF) could be ideal candidates for stem cells and signalling molecules. In this study, bone marrow mesenchymal stem/stromal cells (BM-MSCs) were isolated from patients with type 2 diabetes mellitus (T2DM) and non-diabetic controls. Both cell populations were compared for their clonogenicity, proliferation rates and percentage of MSC populations. Moreover, expression of osteogenic, periodontal markers and IGF axis genes was assessed under basal and osteogenic conditions after 1, 2 and 3 weeks in culture. Levels of IGFBP-2, -3 and -4 in conditioned media were evaluated using ELISA assays. Diabetic and non-diabetic BM-MSCs exhibited similar clonogenic, proliferative and osteogenic potentials. Flow cytometry analysis showed both cell population contained comparable numbers of cells fitting the MSCs phenotype (CD73+, CD90+, CD105+, CD14-, CD19-, CD34-, CD45- and HLA-DR-). Diabetic BM-MSCs expressed lower levels of periodontal markers POSTN and CEMP-1 as well as a number of IGFBPs (IGFBP-2, -3 and -4), although ELISA assays showed similar release levels of these IGFBPs by both diabetic and non-diabetic cells. These molecules could be targeted to enhance the periodontal regeneration potentials of diabetic BM-MSCs. Moreover, both diabetic and non-diabetic cells showed upregulation of IGFBP-2 in their osteogenic cultures along with downregulation of IGF-1 and IGFBP-5, and these molecules could enhance the use of BM-MSCs in bone tissue engineering in general.