Paralysis from spinal injury has long remained untreatable. Could scientific developments get people affected on their feet again sooner than imagined? In a worldwide first, Tel Aviv University researchers have engineered 3D human spinal cord tissues and implanted them in a lab model with long-term chronic paralysis, demonstrating high rates of success 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.
“Our technology is based on taking a small biopsy of belly fat tissue from the patient,” explains Prof. Tal Dvir who’s research team led the study. “This tissue, like all tissues in our body, consists of cells together with an extracellular matrix comprising substances like collagens and sugars. After separating the cells from the extracellular matrix we used genetic engineering to reprogram the cells, reverting them to a state that resembles embryonic stem cells – namely cells capable of becoming any type of cell in the body.”
Petri dish with tissue samples (Photo: Sagol Center for Regenerative Biotechnology)
From the extracellular matrix the researchers produced a personalized hydrogel, that would evoke no immune response or rejection after implantation. They then encapsulated the stem cells in the hydrogel, and in a process that mimics the embryonic development of the spinal cord, turned the cells into 3D implants of neuronal networks containing motor neurons.
Neural net (Photo: Sagol Center for Regenerative Biotechnology)
The human spinal cord implants were then implanted in two different groups of lab models: those who had only recently been paralyzed (the acute model) and those who had been paralyzed for a long time (the chronic model) – equivalent to one year in human terms. Following the implantation, 100% of the lab models with acute paralysis and 80% of those with chronic paralysis regained their ability to walk.
The groundbreaking study was led by 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 Stanley Steyer School of Health Professions at the Sackler Faculty of Medicine, all at Tel Aviv University. The results of the study were published in the prestigious scientific journal Advanced Science.
Visualization of the next stage of the research – human spinal cord implants for treating paralysis (Photo: Sagol Center for Regenerative Biotechnology)
Encouragingly, the model animals underwent a rapid rehabilitation process, at the end of which they could walk quite well. 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.
“Our goal is to produce personalized spinal cord implants for every paralyzed person, enabling regeneration of the damaged tissue with no risk of rejection,” says Prof. Dvir.
Based on the revolutionary organ engineering technology developed at Prof. Dvir’s lab, he teamed up with industry partners to establish Matricelf (matricelf.com) in 2019. The company applies Prof. Dvir’s approach in the aims of making spinal cord implant treatments commercially available for persons suffering from paralysis.
Prof. Dvir, head of Sagol Center for Regenerative Biotechnology, concludes: “We hope to reach the stage of clinical trials in humans within the next few years, and ultimately get these patients back on their feet. The company’s preclinical program has already been discussed with the FDA. 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.”
The research team (from left to right): Dr. Yona Goldshmit, Prof. Tal Dvir and Lior Wertheim (Photo: Sagol Center for Regenerative Biotechnology)
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