Israeli researchers have developed a 3D human spinal cord implants to help paralyzed people walk again


For the first time in the world, researchers from Sagol Center for Regenerative Biotechnology at Tel Aviv University have engineered 3D human spinal cord tissues and implanted them in lab model with long-term chronic paralysis.

The results were highly encouraging: an approximately 80% success rate in restoring walking abilities. Now the researchers are preparing for the next stage of the study: clinical trials in human patients.

They hope that within a few years the engineered tissues will be implanted in paralyzed individuals enabling them to stand up and walk again.

The groundbreaking study was led Prof. Tal Dvir’s research team at the Sagol Center for Regenerative Biotechnology, the Shmunis School of Biomedicine and Cancer Research, and the Department of Biomedical Engineering at Tel Aviv University. The team at Prof. Dvir’s lab includes PhD student Lior Wertheim, Dr. Reuven Edri, and Dr. Yona Goldshmit.

Other contributors included Prof. Irit Gat-Viks from the Shmunis School of Biomedicine and Cancer Research, Prof. Yaniv Assaf from the Sagol School of Neuroscience, and Dr. Angela Ruban from the Steyer School of Health Professions, all at Tel Aviv University.

The results of the study were published in the prestigious scientific journal Advanced Science.

Source: Tel-Aviv University

Journal reference: Wertheim, L., et al. (2022) Regenerating the injured spinal cord at the chronic phase by engineered iPSCsderived 3D neuronal networks. Advanced Science.

The cells would then be reprogrammed to become patient-specific induced pluripotent stem cells (iPSCs) – a cell type used in regenerative medicine that can propagate indefinitely and can be used to replace cells lost to damage or disease.

Meanwhile, the biomaterial undergoes a process to turn it into a personalized hydrogel, which the embryonic-like iPSC cells are then encapsulated in, allowing them to differentiate into a 3D spinal cord network.

Not only does the biomaterial turned hydrogel support the cells, the study explained, but it also constantly adapts and develops, thereby providing a dynamic inductive microenvironment, allowing for the assembly and maturation of a functional spinal cord implant.

Following the successful mimicking of embryonic spinal cord development and the engineering of functional tissue implants, the researchers moved on to testing the therapeutic potential of the 3D spinal cord network, choosing to use mice as the testing model.

THE MICE were divided into two groups – those who had been recently paralyzed (acute), and those who had been paralyzed for at least a year in human terms (chronic).

The mice with acute paralyzation regained the ability to walk within the space of three months after the insertion of the implant, showing significant gains over mice with acute paralysis that had been left untreated.

While the untreated mice did regain partial motor function over time, they showed worse coordination, and a greatly decreased ability to place pressure on the injured foot, among other issues, than those that underwent the implantation of the lab-grown spinal cord.

 Visualization of the next stage of the research - human spinal cord implants for treating paralysis (credit: SAGOL CENTER FOR REGENERATIVE BIOTECHNOLOGY)

Visualization of the next stage of the research – human spinal cord implants for treating paralysis (credit: SAGOL CENTER FOR REGENERATIVE BIOTECHNOLOGY)

Following the success observed in the acute phase of injury, the research team moved on to testing the same theory in the mice with chronic paralyzation, a more clinically relevant model due to the extent of permanent damage to the spinal cord still being unclear during the acute phase of paralysis.

Six weeks after implanting the artificial spinal cord into the mice with chronic paralyzation, the animals showed significant improvement, indicating that the implant had successfully been integrated into the body. Overall, 80% of the mice in the test group regained the ability to walk.

“The model animals underwent a rapid rehabilitation process, at the end of which they could walk quite well,” explained Prof. Dvir. “This is the first instance in the world in which implanted engineered human tissues have generated recovery in an animal model for long-term chronic paralysis, which is the most relevant model for paralysis treatments in humans.”

Following the success seen in the lab trials and the results observed in the mice post-implant, the researchers hope to progress to clinical trials in humans within the next few years. They have already held talks with the FDA regarding the preclinical program.

“Since we are proposing an advanced technology in regenerative medicine, and since at present there is no alternative for paralyzed patients, we have good reason to expect relatively rapid approval of our technology,” he explained.

Based on the revolutionary organ-engineering technology, Dvir teamed up with industry partners to establish Matricelf, founded in 2019. The company applies his approach in their work with the aim of making spinal cord implant treatments commercially available.

 Visualization of the next stage of the research - human spinal cord implants for treating paralysis (credit: SAGOL CENTER FOR REGENERATIVE BIOTECHNOLOGY)

Visualization of the next stage of the research – human spinal cord implants for treating paralysis (credit: SAGOL CENTER FOR REGENERATIVE BIOTECHNOLOGY)

How could this impact the field of medicine?

While the study focused on injured spinal cord specifically, the researchers hope that in the future the same technology could be applied and used to treat a variety of different diseases and injuries such as Parkinson’s, brain trauma, myocardial infarction and age-related macular degeneration, all of which they are currently researching through this technology.

“There are millions of people around the world who are paralyzed due to spinal injury, and there is still no effective treatment for their condition,” Dvir said.

“Individuals injured at a very young age are destined to sit in a wheelchair for the rest of their lives, bearing all the social, financial, and health-related costs of paralysis. Our goal is to produce personalized spinal cord implants for every paralyzed person, enabling regeneration of the damaged tissue with no risk of rejection.”


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