Combinatorial lentiviral gene delivery of pro ‐oligodendrogenic factors for improving myelination of regenerating axons after spinal cord injury

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 remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet‐derived growth factor‐AA and noggin either alone or in combination in a mouse SCI model. AbstractSpinal 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 remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet ‐derived growth factor (PDGF)‐AA and noggin either alone or in combination in a mouse SCI model. Noggin and PDGF‐AA have been identified as factors that enhance recruitment and differentiation of endogenous progenitors to promote myelination. Lentivirus encoding for these factors was delivered from a multichannel 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 recov ery 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 dens...

Source: Biotechnology and Bioengineering - October 27, 2018 Category: Biomedical Science Authors: Dominique R. Smith, Daniel J. Margul, Courtney M. Dumont, Mitchell A. Carlson, Mary K. Munsell, Mitchell Johnson, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea Tags: ARTICLE Source Type: research