A means to accelerate regeneration of neurons and reconstruct the neural circuit in the spine has been discovered, in a further breakthrough for spinal cord injury patients worldwide.
A nanobiomaterial, layered double hydroxide (LDH), has been proven to inhibit the inflammatory environment surrounding spinal cord injuries in mice, in research from Tongji University in Shanghai.
For the first time, the study was also able to identify the underlying genetic mechanism by which LDH works.
The breakthrough in LDH has been hailed by the research team as opening the door for further modification of the therapy which could help produce a clinically-applicable system for spinal cord injury relief in humans.
LDH – which has already been widely explored in biomedical engineering and anti-tumour therapy – has a number of biological properties relevant to spinal cord injury, including good biocompatibility, safe biodegradation and strong anti-inflammatory capability.
“These properties made LDH a really promising candidate for the creation of a much more beneficial microenvironment for spinal cord injury recovery,” says Rongrong Zhu, of the Department of Orthopedics of Tongji Hospital, first author of the study.
In the study, the research team transplanted the LDH into the injury site of mice, and found that the nanobiomaterial had significantly accelerated neural stem cells migration, neural differentiation, activation of channels for neuron excitation, and induction of action potential (nerve impulse) activation.
The mice were also found to have significantly improved locomotive behaviour compared to the control group of mice.
In addition, when the LDH was combined with Neurotrophin-3 (NT3), a protein that encourages the growth and differentiation of new neurons, the mice experienced even better recovery effects than the LDH on its own.
Then, via transcriptional profiling, or analysis of gene expression of thousands of genes at once, the researchers were able to identify how the LDH performs its assistance.
They found that once LDH is attached to cell membranes, it provokes greater activation of the “transforming growth factor-β receptor 2” (TGFBR2) gene, decreasing production of the white blood cells that enhance inflammation and increasing production of the white blood cells that inhibit inflammation.
Upon application of a chemical that inhibits TGFBR2, they found the beneficial effects were reversed.
The understanding of how LDH performs these effects should now allow the researchers to adjust the therapy to enhance its performance and to finally create a comprehensive therapeutic system for spinal cord injuries – combining these biomaterials with neurotrophic factors like NT3-that can be used in clinical application on people.
