Front Cell Dev Biol: Gene therapy promotes nerve regeneration

December 19, 2020 // --- spinal cord injury (SCI) usually leads to disability and seriously affects the quality of life.
, despite decades of research on SCI post-axon progenigenic regeneration, most interventions have not yet been translated into clinical therapies.
of the difficulties of SCI treatment may be the permanent loss of nerve function due to the loss of many neurons during the injury.
in the latest issue of Frontiers in Cell and Developmental Biology, published on December 16, 2020, a team led by Professor Chen Gong of Jinan University reported on an innovative gene therapy that uses local glial cells to regenerate functional new neurons.
unlike classical methods, the study focused on promoting axon regeneration or transplanting external stem cells, and Professor Chen and his team used internal glial cells in the damaged spinal cord to directly convert them into functional new neurons.
, Chen's team published a series of articles demonstrating that overextendation of neuroretrophic factor NeuroD1 or NeuroD1 plus Dlx2 can convert reactive astrological glial cells into neurons in mouse models of Alzheimer's disease, ischemia stroke, or Huntington's disease.
they recently pushed the technique to non-human primates by proving that reactive astrological glial cells in the macaque brain are directly converted into neurons.
(Photo Source: www.pixabay.com) In this work, Professor Chen and his team further extended their neurogeneration techniques from the brain to the spinal cord.
they first demonstrated that NeuroD1's over-expression in reactive astrocytes by transretroviral division can successfully convert astrological glial cells into neurons in the damaged spinal cord.
the advantage of using retrovirus is that they express gmostrains only in divided glial cells, such as NeuroD1, rather than in undi divided neurons, eliminating the possibility of direct NeuroD1 expression in existing neurons.
In order to improve the efficiency of neuronal conversion and pave the way for future translation applications, Professor Chen's team further developed adeno-related virus systems (AAVs) to transfer NeuroD1 to divided and non-dividing astrocytes under the control of GFAP, a star cell promoter, and to confirm the transformation of star glial cells directly into neurons in the spinal cord.
AAV vectors are commonly used in gene therapy because of their relatively low immunogenicity and high efficiency in spreading in various tissues, including nerve tissue.
Professor Chen's team found that individual NeuroD1 produced mainly excitable glutamate-energy neurons, while adding another transcription factor, Dlx2, significantly increased the proportion of inhibitory GABA energy neurons, suggesting that different combinations of transcription factors could produce different neuron subtypes.
factors that affect the fate of neurons after conversion are the environment.
by injecting the same NeuroD1 vector into the mouse cortique or spinal cord.
month, they found that the transformed neurons of astrological glial cells transplanted in the cortical corticals showed cortical neuronal markers, but no spinal cord markers.
contrary, neurons transformed by spinal as astrological glial cells show spinal neuronal markers, but no cortical markers, indicating the importance of local environments in shaping the fate of neurons.
(Bioon.com) Source: Neuroregenerative Gene therapy Source: Brendan Puls et al. Regeneration of Functional Neurons After Spinal Cord Injury via in situ NeuroD1-Mediated Astrocyte-to-Neuron Conversion. Front. Cell Dev. Biol., 16 December 2020. doi.org/10.3389/fcell.2020.591883。