Abstract
Background: Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients. Objective: We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation. Materials and methods: DPMSCs were isolated from patients with healthy teeth (n = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control. Results: VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-β1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control. Conclusions: The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.
Highlights
Mesenchymal stem cells derived from the dental pulp (DPMSC) possess a high capacity for differentiation and regeneration
The isolated DPMSC showed MSC-like morphological characteristics (Figure 1A) and were positive for mesenchymal stem cell markers CD90, CD73, and CD105, and negative for hematopoietic markers CD34, CD45-APC, and MHC class II antigen HLA-DR-PE
The remaining growth factors constituted less than 5 pg/mL
Summary
Mesenchymal stem cells derived from the dental pulp (DPMSC) possess a high capacity for differentiation and regeneration. They exhibit greater proliferation than other stem cells. The dental pulp is a readily accessible source of postnatal stem cells These properties facilitate their ex vivo expansion and make them an attractive choice of source for mesenchymal stem cells. A major advantage of DPMSC is its ability to modulate the host’s immune system, preventing any significant adverse reaction [6] Their inherent homing ability towards tissues with injury and pathology including cancers have led to an interest in their application as a drug delivery agent [7]. Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis.
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