Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats

Cell-based transplantation strategies possess great potential for spinal cord injury (SCI) repair. Basic fibroblast growth factor (bFGF) has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI. Human dental pulp stem cells (DPSCs) are abundant stem cells with low immune rejection, which can be considered for cell replacement therapy. The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements (5HRE) using an adeno-associated virus (AAV-5HRE-bFGF-DPSCs) in SCI repairing model. In this study, DPSCs were revealed to differentiate into CD13+ pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13+ pericytes to vascular endothelial cells. The re-attachment of CD13+ pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance. As a result, increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved. Thus, this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.
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Highlights • ) 5HRE-bFGF-DPSCs secrete bFGF in a hypoxia dependent manner, making the administration more precise. • CD13+ pericyte regulate vascular diameter and promote the recovery of hypoxia microenvironment via DDC-5HT-5HT-1B in SCI. • 5HRE-bFGF-DPSCs can differentiate into CD13+ pericyte to compensate for the mass death of CD13+ pericyte after SCI. • 5HRE-bFGF-DPSCs promote CD13+ pericyte adhesion to vascular endothelial cell by secreting bFGF through N-cadherin. • 5HRE-bFGF-DPSCs promote the recovery of SCI by restoring hypoxic microenvironment and inhibit autophagy pathway.