Human Dental Pulp Mesenchymal Stem Cell-Derived Soluble Factors Combined with a Nanostructured Scaffold Support the Generation of a Vascular Network In Vivo

Abstract

Among all strategies directed at developing new tools to support re-vascularization of damaged tissues, the use of pro-angiogenic soluble factors, derived from mesenchymal stem cells (MSCs), appears a promising approach for regenerative medicine. Here, we compared the feasibility of two devices, generated by coupling soluble factors of human dental pulp mesenchymal stem cells (DPSCs), with a nanostructured scaffold, to support angiogenesis once transplanted in mice. DPSCs were obtained from impacted wisdom tooth removal, usually considered surgical waste material. After 28 days, we verified the presence of active blood vessels inside the scaffold through optical and scansion electron microscopy. The mRNA expression of surface antigens related to macrophage polarization (CD68, CD80, CD86, CD163, CD206), as well as pro-angiogenic markers (CD31, CD34, CD105, Angpt1, Angpt2, CDH5) was evaluated by real-time PCR. Our results demonstrate the capability of DPSC–scaffold and DPSC soluble factors–scaffold to support angiogenesis, similarly to adipose stem cells, whereas the absence of blood vessels was found in the scaffold grafted alone. Our results provide evidence that DPSC-conditioned medium can be proposed as a cell-free preparation able to support angiogenesis, thus, providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

How to make full use of dental pulp stem cells: an optimized cell culture method based on explant technology

“…Although human clinical studies on DPSC are still relatively few due to reasons such as incompletely confirmed safety and cost of treatment, animal experiments on DPSC have been relatively abundant, which amply demonstrates their promising application in tissue engineering. Barone et al implanted DPSC and cell scaffolds into nude mice and found that the experimental group obtained better in vivo vascular network generation ( Barone et al, 2023 ). Yamaguchi et al applied DPSC intravenously to treat mice in an ischemia-reperfusion myocardial injury model and found that apoptosis and inflammation in cardiomyocytes were significantly suppressed ( Yamaguchi et al, 2015 ).…”