title: Platelet-Derived Growth Factor Regulates Proliferation and Inflammation of Olfactory Mesenchymal Cells In Vitro
Creators: name: Barker, Matthew W
Publisher: name: Griffith University
Year: 2023
Subjects: subject: fibroblast
subject: spinal cord injury
subject: PDGF
subject: OEC

description: Recent estimates put the global incidence of spinal cord injury (SCI) at around 900,000 cases annually. SCI is a lifelong condition with no cure, and there is an urgent need for novel therapies to stimulate regeneration. Olfactory neurons are subject to continuous environmental ablation, and as such there exists within the olfactory system a range of neuroregenerative cells which support neuronal regeneration and maintain the neuronal population in the face of cellular attrition. By using the patient’s own olfactory cells and transplanting them to the site of injury (i.e., autologous transplantation) we can harness their neuroregenerative properties to repair the injured spinal cord while alleviating potential transplant rejection. While these therapies show a great deal of promise, they currently cannot offer consistent, reproducible outcomes, highlighting the need for more research and optimisation before they are ready for clinical applications. Olfactory ensheathing cells (OECs) are amongst the most prominent cells of interest in regenerative therapies for their ability to clear the injury site through phagocytosis of cell debris and secretion of neurotrophic factors. However, while OECs clearly have neuroregenerative effects, generating large populations of pure OECs for transplantation is difficult. OECs show limited proliferation in monoculture in vitro and purification methods used to separate OECs from other olfactory cells are sorely lacking. Given the difficulties of generating pure OEC cultures, co-transplant therapies combining OECs with other regenerative cell types from the olfactory system become more appealing. Mesenchymal stromal cells (MSCs) are a rapidly proliferating cell type that has shown promise for cell transplantation due to their capacity to generate extracellular matrix (ECM) proteins and regulate inflammatory response. Additionally, OECs show enhanced proliferation when cultured alongside MSCs in vitro. There is also evidence to suggest that the distinct but compatible functions of OECs and MSC may have synergistic effects for cell transplantation. As such, OEC-MSC co-transplantation may improve functional outcomes for cell transplantation, not only by stimulating the proliferation of OECs but also through the synergistic effects of OEC-MSC neuroregenerative function. In fact, it seems that many of the clinical trials that have successfully demonstrated the use of OEC transplantation may have been as a result of combined OEC-MSC treatments. To date, there are few studies that have utilised high purity OECs for cell transplantation. Previous studies have either used whole olfactory tissue, used limited cell purification, or simply acknowledged that OECs made up a relatively small component of their treatment. This lack of consistency in the therapeutic doses of cells given to patients remains one of the largest problems facing researchers investigating OECs for spinal cord therapy and may be one of the biggest contributors to a lack of reproducibility in terms of functional outcomes for patients.