Dental pulp stem cells: Novel cell-based and cell-free therapy for peripheral nerve repair

Abstract

The regeneration of peripheral nerves comprises complicated steps involving a set of cellular and molecular events in distal nerve stumps with axonal sprouting and remyelination. Stem cell isolation and expansion for peripheral nerve repair (PNR) can be achieved using a wide diversity of prenatal and adult tissues, such as bone marrow or brain tissues. The ability to obtain stem cells for cell-based therapy (CBT) is limited due to donor site morbidity and the invasive nature of the harvesting process. Dental pulp stem cells (DPSCs) can be relatively and simply isolated from the dental pulps of permanent teeth, extracted for surgical or orthodontic reasons. DPSCs are of neural crest origin with an outstanding ability to differentiate into multiple cell lineages. They have better potential to differentiate into neural and glial cells than other stem cell sources through the expression and secretion of certain markers and a range of neurotropic factors; thus, they should be considered a good choice for PNR using CBT. In addition, these cells have paracrine effects through the secretion of neurotrophic growth factors and extracellular vesicles, which can enhance axonal growth and remyelination by decreasing the number of dying cells and activating local inhabitant stem cell populations, thereby revitalizing dormant or blocked cells, modulating the immune system and regulating inflammatory responses. The use of DPSC-derived secretomes holds great promise for controllable and manageable therapy for peripheral nerve injury. In this review, up-to-date information about the neurotrophic and neurogenic properties of DPSCs and their secretomes is provided.

Keywords: Dental pulp stem cells; Secretomes; Cell-based therapy; Cell-free therapy; Peripheral nerve injury

Core tip: The distinct developmental pathway of dental pulp stem cells (DPSCs) from neural crest cells results in a cell type that can be participate in neural tissue regeneration. The efficacy of using DPSCs for peripheral nerve repair (PNR) is strongly influenced by boosting trophic factors that promote axonal growth and regeneration and provide direct and indirect protection against cell death. Recently, encouraging results from different studies indicate that DPSC secretomes have reparative and protective properties comparable with their cellular counterparts in PNR. The use of DPSC secretomes as a safe and possibly more valuable substitute for cell-based therapy approaches is a novel therapeutic perspective.