Sponge-mediated lentivirus delivery to acute and chronic spinal cord injuries

Journal of Controlled Release : Official Journal of the Controlled Release Society
Aline M ThomasLonnie D Shea

Abstract

The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sp...Continue Reading

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Citations

Aug 18, 2016·Biotechnology and Bioengineering·Nisha R IyerShelly E Sakiyama-Elbert
Mar 31, 2017·Journal of Neural Engineering·Robert B ShultzYinghui Zhong
Feb 9, 2017·Tissue Engineering. Part B, Reviews·Justin L MadrigalEduardo A Silva
Aug 30, 2020·Neural Regeneration Research·Robert B Shultz, Yinghui Zhong
Dec 6, 2018·Nature Reviews. Rheumatology·Magali Cucchiarini, Henning Madry
Feb 2, 2019·Bioconjugate Chemistry·Douglas Steinhauff, Hamidreza Ghandehari

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