English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Cell replacement therapy is one potential avenue for central nervous system (CNS) repair. However, transplanted stem cells may not contribute to long-term recovery of the damaged CNS unless they are engineered for functional advantage. To fine tune regenerative capabilities, we developed a human neural cell line expressing L1, a regeneration-conducive adhesion molecule, under the control of a doxycycline regulatable Tet-off promoter. Controlled expression of L1 is desired because overexpression after regenerative events may lead to adverse consequences. The regulated system was tested in several cell lines, where doxycycline completely eliminated green fluorescent protein or L1 expression by 3-5 days in vitro. Increased colony formation as well as decreased proliferation were observed in H9NSCs without doxycycline (hL1-on). To test the role of L1 in vivo after acute compression spinal cord injury of immunosuppressed mice, quantum dot labeled hL1-on or hL1-off cells were injected at three sites: lesion; proximal; and caudal. Mice transplanted with hL1-on cells showed a better Basso Mouse Scale score, when compared to those with hL1-off cells. As compared to the hL1-off versus hL1-on cell transplanted mice 6 weeks post-transplantation, expression levels of L1, migration of transplanted cells, and immunoreactivity for tyrosine hydroxylase were higher, whereas expression of chondroitin sulfate proteoglycans was lower. Results indicate that L1 expression is regulatable in human stem cells by doxycycline in a nonviral engineering approach. Regulatable expression in a prospective nonleaky Tet-off system could hold promise for therapy, based on the multifunctional roles of L1, including neuronal migration and survival, neuritogenesis, myelination, and synaptic plasticity.

Analysis of Human Embryonic Stem Cells with Regulatable Expression of the Cell Adhesion Molecule L1 in Regeneration after Spinal Cord Injury