Combinatorial lentiviral gene delivery of pro-oligodendrogenic factors to improve myelination of regenerating axons after spinal cord injury

• Published in: Biotechnology and bioengineering 2018-10, Vol.116 (1), p.155-167
• Main Authors: Smith, Dominique R., Margul, Daniel J., Dumont, Courtney M., Carlson, Mitchell A., Munsell, Mary K., Johnson, Mitchell, Cummings, Brian J., Anderson, Aileen J., Shea, Lonnie D.
• Format: Article
• Language: English
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.26838

Spinal cord injury (SCI) results in paralysis below the injury and strategies are being developed that support axonal regrowth, yet recovery lags, in part, because many axons are not re-myelinated. Herein, we investigated strategies to increase myelination of regenerating axons by over-expression of platelet-derived growth factor-AA (PDGF) and noggin either alone or in combination in a mouse SCI model. Noggin and platelet-derived growth factor aa (PDGF) have been identified as factors that enhance recruitment and differentiation of endogenous progenitors to promote myelination. Lentivirus encoding for these factors were delivered from a multi-channel bridge, which we have previously shown creates a permissive environment and supports robust axonal growth through channels. The combination of noggin + PDGF enhanced total myelination of regenerating axons relative to either factor alone, and importantly, enhanced functional recovery relative to the control condition. The increase in myelination was consistent with an increase in oligodendrocyte-derived myelin, which was also associated with a greater density of cells of an oligodendroglial lineage relative to each factor individually and control conditions. These results suggest enhanced myelination of regenerating axons by noggin + PDGF that act on oligodendrocyte-lineage cells post-SCI, which ultimately led to improved functional outcomes.