Osteogenically differentiated mesenchymal stem cells promote the apoptosis of human umbilical vein endothelial cells in vitro.
Miaomiao ChaiMingli JiangCe GuQiaohui LuYi ZhouZiyang JinYan ZhouWensong TanPublished in: Biotechnology and applied biochemistry (2021)
The absence of blood vessels in tissue engineered bone often leads to necrosis of internal cells after implantation, ultimately affecting the process of bone repair. Herein, mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to induce osteogenesis and angiogenesis. Based on the findings, the number of HUVECs in the coculture system increased in the growth medium group, but decreased in the osteogenic induction medium (OIM) group. Considering that the paracrine effects of MSCs had changed, we tested the genes expression of osteogenically differentiated MSCs. The expression of osteogenic genes in MSCs increased during osteogenesis. Further, the expression levels of pigment epithelial-derived factor (PEDF) gene and protein, an antivascular factor, were also increased. To verify whether MSCs promote HUVECs apoptosis via PEDF, PEDF was silenced via siRNA. The conditioned medium of differentiated MSCs with PEDF silencing significantly improved the proliferation and apoptosis of HUVECs. Based on further experiments, PEDF mediated the apoptosis and proliferation of HUVECs through p53, BAX/BCL-2, FAS, and c-Caspase-3. However, when PEDF was silenced with siRNA, the osteogenic potential of MSCs was affected. The results of this study provide a theoretical basis for the construction of prevascularized bone tissues in vitro.
Keyphrases
- mesenchymal stem cells
- cell cycle arrest
- umbilical cord
- endoplasmic reticulum stress
- endothelial cells
- induced apoptosis
- cell death
- oxidative stress
- poor prognosis
- bone marrow
- bone mineral density
- pi k akt
- cell therapy
- genome wide
- signaling pathway
- bone regeneration
- binding protein
- gene expression
- genome wide identification
- stem cells
- soft tissue
- bone loss
- vascular endothelial growth factor
- cancer therapy
- high glucose
- small molecule
- drug delivery
- bioinformatics analysis
- hyaluronic acid
- dna methylation