preserving-vivo-tissue-complexity-mice-olfactory-nervous-system-model

Preserving <em>In Vivo</em> Tissue Complexity in a Mice Olfactory Nervous System Model Using Whole-Mount Analysis for Studying Neural Regeneration

In the era of three-dimensional (3D) imaging, standard immunohistochemistry has been recognized as highly limited in studies of pathology and complex ...

Griffith University

The glial cells of the primary olfactory nervous system, olfactory ensheathing cells (OECs), are unusual in that they rarely form tumors. Only 11 cases, all of which were benign, have been reported to date. In fact, the existence of OEC tumors has been debated as the tumors closely resemble schwannomas (Schwann cell tumors), and there is no definite method for distinguishing the two tumor types. OEC transplantation is a promising therapeutic approach for nervous system injuries, and the fact that OECs are not prone to tumorigenesis is therefore vital. However, why OECs are so resistant to neoplastic transformation remains unknown. The primary olfactory nervous system is a highly dynamic region which continuously undergoes regeneration and neurogenesis throughout life. OECs have key roles in this process, providing structural and neurotrophic support as well as phagocytosing the axonal debris resulting from turnover of neurons. The olfactory mucosa and underlying tissue is also frequently exposed to infectious agents, and OECs have key innate immune roles preventing microbes from invading the central nervous system. It is possible that the unique biological functions of OECs, as well as the dynamic nature of the primary olfactory nervous system, relate to the low incidence of OEC tumors. Here, we summarize the known case reports of OEC tumors, discuss the difficulties of correctly diagnosing them, and examine the possible reasons for their rare incidence. Understanding why OECs rarely form tumors may open avenues for new strategies to combat tumorigenesis in other regions of the nervous system.

Why are olfactory ensheathing cell tumors so rare?

Olfactory ensheathing cells (OECs), the glial cells of the primary olfactory nervous system, support the natural regeneration of the olfactory nerve that occurs throughout life. OECs thus exhibit unique properties supporting neuronal survival and growth. Transplantation of OECs is emerging as a promising treatment for spinal cord injury; however, outcomes in both animals and humans are variable and the method needs improvement and standardization. A major reason for the discrepancy in functional outcomes is the variability in survival and integration of the transplanted cells, key factors for successful spinal cord regeneration. Here, we review the outcomes of OEC transplantation in rodent models over the last 10 years, with a focus on survival and integration of the transplanted cells. We identify the key factors influencing OEC survival: injury type, source of transplanted cells, co-transplantation with other cell types, number and concentration of cells, method of delivery, and time of transplantation after the injury. We found that two key issues are hampering optimization and standardization of OEC transplantation: lack of (1) reliable methods for identifying transplanted cells, and (2) three-dimensional systems for OEC delivery. To develop OEC transplantation as a successful and standardized therapy for spinal cord injury, we must address these issues and increase our understanding of the complex parameters influencing OEC survival.

Survival and Integration of Transplanted Olfactory Ensheathing Cells are Crucial for Spinal Cord Injury Repair: Insights from the Last 10 Years of Animal Model Studies.

Cell transplantation constitutes an important avenue for development of new treatments for spinal cord injury (SCI). These therapies are aimed at supporting neural repair and/or replacing lost cells at the injury site. To date, various cell types have been trialed, with most studies focusing on different types of stem cells or glial cells. Here, we review commonly used cell transplantation approaches for spinal cord injury (SCI) repair, with focus on transplantation of olfactory ensheathing cells (OECs), the glial cells of the primary olfactory nervous system. OECs are promising candidates for promotion of neural repair given that they support continuous regeneration of the olfactory nerve that occurs throughout life. Further, OECs can be accessed from the nasal mucosa (olfactory neuroepithelium) at the roof of the nasal cavity and can be autologously transplanted. OEC transplantation has been trialed in many animal models of SCI, as well as in human clinical trials. While several studies have been promising, outcomes are variable and the method needs improvement to enhance aspects such as cell survival, integration, and migration. As a case study, we include the approaches used by our team (the Clem Jones Centre for Neurobiology and Stem Cell Research, Griffith University, Nathan, QLD, Australia) to address the current problems with OEC transplantation and discuss how the therapeutic potential of OEC transplantation can be improved. Our approach includes discovery research to improve our knowledge of OEC biology, identifying natural and synthetic compounds to stimulate the neural repair properties of OECs, and designing three-dimensional cell constructs to create stable and transplantable cell structures.

Article	Year
Why are olfactory ensheathing cell tumors so rare? Cancer cell international\| PubMed ID: 31632194	2019
Survival and Integration of Transplanted Olfactory Ensheathing Cells are Crucial for Spinal Cord Injury Repair: Insights from the Last 10 Years of Animal Model Studies. Cell transplantation\| PubMed ID: 31726863	2019
Optimizing Olfactory Ensheathing Cell Transplantation for Spinal Cord Injury Repair. Journal of neurotrauma\| PubMed ID: 32056492	2020
The link between olfactory ensheathing cell survival and spinal cord injury repair: a commentary on common limitations of contemporary research. Neural regeneration research\| PubMed ID: 32246630	2020

Ronak Reshamwala

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