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

Abstract

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.

High-Yield Mucosal Olfactory Ensheathing Cells Restore Loss of Function in Rat Dorsal Root Injury

“…OECs can be derived from the olfactory bulb and the olfactory mucosa [ 38 , 39 ]. Most experimental transplantation studies, especially those with a positive outcome, have used OECs of bulbar origin (bOECs) in experimental injury models [ 5 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 40 , 41 ] and clinical applications [ 30 , 42 , 43 , 44 ]. In our previous studies comparing the transplantation of OECs from the bulb and mucosa into corticospinal tract lesions, only bOECs induced axonal regeneration across the lesion [ 45 , 46 ].…”

Transplantation of sh-miR-199a-5p-Modified Olfactory Ensheathing Cells Promotes the Functional Recovery in Rats with Contusive Spinal Cord Injury

“…In this study, although we cannot measure the proportion of survived OECs at 1 wk after transplantation, our results indicated that OEC transplantation promoted the functional recovery in SCI rats; moreover, modified OECs showed a better neural repair effect. A recent review pointed out that OECs can survive within 1 wk to 1 yr after transplantation 41 . Furthermore, we paid more attention to the gene regulation effects of OECs in SCI rats at 1 wk after transplantation in this study; therefore, we did not explore the survival of OECs after 1 wk.…”

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease

“…Due to their capacity to remove cell debris and to promote neuronal regeneration, both SCs and OECs have been explored as candidates to treat CNS injuries, in particular spinal cord injury, via cell transplantation therapies, with variable outcomes (reviewed by Kocsis and Waxman, 2007;Kanno et al, 2015;Yao et al, 2018;Reshamwala et al, 2019). Transplantation of these glia has also been trialed for improving the rate of PNS regeneration which is ∼1 mm/day (Sulaiman and Gordon, 2000) and for repairing large peripheral nerve injuries (Chen et al, 2006;Radtke et al, 2011;Rodrigues et al, 2012;Xia et al, 2019).…”