Versatile subtypes of pericytes and their roles in spinal cord injury repair,bone development and repair

Vascular regeneration is a challenging topic in tissue repair. As one of the important components of the neurovascular unit(NVU),pericytes play an essential role in the maintenance of the vascular network of the spinal cord. To date, subtypes of pericytes have been identified by various markers, namely the PDGFR-β, Desmin, CD146, and NG2, each of which is involved with spinal cord injury(SCI) repair. In addition, pericytes may act as a stem cell source that is important for bone development and regeneration, whilst specific subtypes of pericyte could facilitate bone fracture and defect repair. One of the major challenges of pericyte biology is to determine the specific markers that would clearly distinguish the different subtypes of pericytes, and to develop efficient approaches to isolate and propagate pericytes. In this review, we discuss the biology and roles of pericytes, their markers for identification, and cell differentiation capacity with a focus on the potential application in the treatment of SCI and bone diseases in orthopedics.

A shear-thinning,ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis

Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.

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.