Profiling the Secretome of Human Stem Cells from Dental Apical Papilla

Abstract

Recent studies have shown that secretion of bioactive factors from mesenchymal stem cells (MSCs) plays a primary role in MSC-mediated therapy; especially for bone marrow-derived MSCs (BMSCs). MSCs from dental apical papilla (SCAPs) are involved in root development and may play a critical role in the formation of dentin and pulp. Bioactive factors secreted from SCAPs actively contribute to their environment; however, the SCAPs secretome remains unclear. To address this and gain a deeper understanding of the relevance of SCAPs secretions in a clinical setting, we used isobaric chemical tags and high-performance liquid chromatography with tandem mass spectrometry to profile the secretome of human SCAPs and then compared it to that of BMSCs. A total of 2,046 proteins were detected from the conditioned medium of SCAPs, with a false discovery rate of less than 1.0%. Included were chemokines along with angiogenic, immunomodulatory, antiapoptotic, and neuroprotective factors and extracellular matrix (ECM) proteins. The secreted levels of 151 proteins were found to differ by at least twofold when BMSCs and SCAPs were compared. Relative to BMSCs, SCAPs exhibited increased secretion of proteins that are involved in metabolic processes and transcription and lower levels of those associated with biological adhesion, developmental processes, and immune function. In addition, SCAPs secreted significantly larger amounts of chemokines and neurotrophins than BMSCs, whereas BMSCs secreted more ECM proteins and proangiogenic factors. These results may provide important clues regarding the molecular mechanisms associated with tissue regeneration and how they differ between cell sources.

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

“…Comparing MSCs from apical papilla-CM to bone marrow MSC-CM, proteins responsible for angiogenesis, immunomodulation, chemotaxis, neuroprotection, antiapoptosis, and extracellular matrix formation were detected in both CM. A significant difference in the levels of 151 of the detected proteins was however noticeable between the two cell sources, where MSCs from apical papilla-CM was associated with higher levels of proteins related to metabolic processes and transcription in addition to chemokines and neurotrophins and lower levels of proteins responsible for adhesion, immunomodulation, angiogenesis, and extracellular matrix proteins [104]. MSCs from the apical papilla-CM, dental follicle MSC-CM, and dental pulp MSC-CM showed a common expression of 174 cytokines.…”

Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3

“…At specific time points (0 h, 24 h, 48 h, 72 h, 96 h), the cultures were supplemented with cell counting kit-8 (CCK-8) solution (Dojindo, Japan) and incubated for 1 h at 37 °C. Cell proliferation was measured at a wavelength of 450 nm by a microplate reader 32 .…”

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

“…Subsequently, it has been shown that, under serum, glucose, and oxygen deprivation (SGOD) conditions, SCAP release higher numbers and amounts of proangiogenic factors (Angiogenin, IGFBP-3, and VEGF) and lower amounts of antiangiogenic factors (Serpin-E1, TIMP-1, and TSP-1) in comparison with SOD or SD alone, providing insights into the optimal preconditioning strategies for SC-based treatment of damaged/ischemic tissues [58]. Most recently, SCAP secretome has been extensively profiled [131]; it was found that a total of 2,046 proteins are released, including chemokines, angiogenic, immunomodulatory, antiapoptotic, and neuroprotective factors, and ECM proteins. SCAP secreted significantly larger amounts of chemokines and neurotrophins than BMMSCs, whereas BMMSCs secreted more ECM proteins and proangiogenic factors.…”