Combining cell transplantation and gene therapy to enhance axonal outgrowth in...

Image source: Adobe Stock/MMPhoto21 

News • Neuroscience, biomedical technology

Combining cell transplantation and gene therapy to enhance axonal outgrowth in the central nervous system

A study led by Dr. Ryosuke Tsuchimochi and Professor Jun Takahashi examined the effects of combining cell transplantation and gene therapy for axonal outgrowth in the central nervous system.

The authors demonstrated the potential of this combinatorial therapy for promoting axonal regeneration in patients with central nervous system injuries. The study has been recently published in the journal Stem Cell Reports.

Stroke and traumatic brain/spinal cord injuries often damage the corticospinal tract (CST), composed of descending axonal tracts from the motor cortex down the spinal cord, that innervates motor neurons to activate skeletal muscles for controlling voluntary movements. Pharmacological and surgical interventions, in conjunction with rehabilitation, can maintain some lost motor functions, but patients with such acute neural injuries often suffer from lifelong severe motor impairment.

Cell replacement therapy—the implantation of new neurons into damaged brain regions—is viewed as a last hope that could help patients recover sufficient motor functions to live a normal life. The research team previously demonstrated that brain tissues transplanted into injured mouse brains could find their way to the CST and spinal cord but believed that further optimization of the host environment was necessary to promote CST reconstruction and functional recovery. 

Optimizing the host environment by gene therapy will support the cell therapy.
Optimizing the host environment by gene therapy will support the cell therapy.

Image source: Kyoto University 

The researchers decided to test the combination of cell transplantation and gene therapy to optimize the host environment in the central nervous system to enhance axonal extension and promote outgrowth by the transplanted brain cells. Specifically, the researchers used an adeno-associated virus (AAV) to deliver a transgene encoding L1CAM, one of four axon guidance molecules tested in the study, into the host mouse motor cortex before the implanting of embryonic brain tissue.

Among the axon guidance molecules tested, L1CAM was the most effective at promoting axonal extensions by the implanted embryonic cerebral grafts. Indeed, axons from the donor tissue were observed to reach the cervical spinal cord in animals with L1CAM transgene expression, as early as one week following cell transplantation and continued to survive up to three months at the time of analysis.

The study highlights the potential of combinatorial therapy for promoting axonal regeneration in patients with central nervous system injuries. Further research is needed to explore the safety and efficacy of this approach in clinical settings.


Source: Kyoto University

12.04.2023

Read all latest stories

Related articles

Article •

Philips and Neuronexus to research next generation deep brain stimulation device

NeuroNexus Technologies and Philips Research announced that they have signed a joint research agreement to develop next-generation deep brain stimulation devices with the ambition to improve the…

Photo

News • LDIR in neurology

The therapeutic potential of low-dose radiation for TBI and stroke

Neuroscientists recently discovered that low-dose ionizing radiation (LDIR) can reduce lesion size and reverse motor deficits in TBI and ischemic stroke mice, demonstrating its therapeutic potential.

Photo

News • In between neurons and astrocytes

Neuroscientists discover new kind of brain cell

It had long been recognized that the brain was made up of two types of cells, neurons and glial cells. Now, neuroscientists discovered an additional type - with huge implications for brain disorders.

Related products

Subscribe to Newsletter