Angiogenic Effects of Secreted Factors from Periodontal Ligament Stem Cells

Abstract

Periodontal disease is a chronic inflammation of tooth-supporting tissues, and the destruction of these tissues results in tooth loss. Regeneration of periodontal tissues is the ultimate goal of periodontal treatment. We previously reported that transplantation of conditioned medium (CM) of periodontal ligament stem cells (PDLSCs) demonstrated the enhancement of periodontal tissue regeneration, compared to CM from fibroblasts (Fibroblast-CM). We hypothesized that the angiogenic effects of PDLSC-CM might participate in the enhanced wound healing of periodontal tissues. The aim of this study was to investigate the effect of PDLSC-CM on the functions of endothelial cells. PDLSCs were cultured from periodontal ligament tissues obtained from healthy volunteers. Human gingival epithelial cells, dermal fibroblasts, osteoblasts, and umbilical vein endothelial cells (HUVECs) were purchased from commercial sources. The functions of endothelial cells were examined using immunostaining of Ki67, observation of nuclear fragmentation and condensation (apoptosis), and network formation on Matrigel. Vascular endothelial cell growth factor (VEGF) level was measured using an ELISA kit. HUVECs demonstrated higher cell viability in PDLSC-CM when compared with those in Fibroblast-CM. HUVECs demonstrated a higher number of Ki67-positive cells and lower apoptosis cells in PDLSC-CM, compared to Fibroblast-CM. Additionally, HUVECs formed more capillary-like structures in PDLSC-CM than Fibroblast-CM. PDLSC-CM contained higher levels of angiogenic growth factor, VEGF, than Fibroblast-CM. Our results showed that PDLSC-CM increased cell viability, proliferation, and capillary formation of HUVECs compared to Fibroblast-CM, suggesting the angiogenic effects of PDLSC-CM, and the effect is a potential regenerative mechanism of periodontal tissues by PDLSC-CM.

Salvadora persica: Nature’s Gift for Periodontal Health

“…The oriented periodontal ligament fibers must then be attached to newly generated alveolar bone and cementum tissue, which is one of the most challenging processes in periodontal regeneration [115]. Numerous groups have widely discussed the significant potential of periodontal regeneration with remarkable clinical success thru mechanisms of regeneration for bone, cementum, and PDL via mobilization of endogenous stem cells from their niche areas, transplantation of exogenous stem cells targeting periodontal defects, or growth/angiogenic factor-mediated regenerative modulation [115][116][117]. Numerous mesenchymal stem cell (MSC) types persist and are responsible for tissue homeostasis, acting as a reservoir of renewable stem/progenitor cells to produce other essential cells throughout adulthood [118].…”

Human Periodontal Ligament Stem Cell and Umbilical Vein Endothelial Cell Co-Culture to Prevascularize Scaffolds for Angiogenic and Osteogenic Tissue Engineering

“…As a type of MSCs isolated from periodontal tissues, hPDLSCs have multiple characteristic advantages. Studies have indicated that PDLSCs can differentiate into periodontal tissue-forming cells, such as cementoblasts, osteoblasts, and fibroblasts [17]. Additionally, in vivo studies have demonstrated successful periodontal tissue regeneration after transplanting hPDLSCs into alveolar defects [17].…”

“…Studies have indicated that PDLSCs can differentiate into periodontal tissue-forming cells, such as cementoblasts, osteoblasts, and fibroblasts [17]. Additionally, in vivo studies have demonstrated successful periodontal tissue regeneration after transplanting hPDLSCs into alveolar defects [17]. In addition, hPDLSCs reveal robust self-renewal ability which is higher than that of hBMSCs and human dental pulp stem cells [18].…”

Influence of Periodontal Ligament Stem Cell-Derived Conditioned Medium on Osteoblasts

“…Periodontitis is a bacterially-induced chronic inflammatory disease of the periodontium [1]. The accumulation of dental plaque microorganisms can result in the progressive and irreversible destruction of tooth-supporting tissues, including gingiva, periodontal ligament, cementum, and alveolar bone.…”