Summary: Researchers engineered functional human spinal cord tissue from cells and human materials which, when implanted into animal models of spinal cord injury, restored walking ability in 80% of the test subjects.
Source: Tel Aviv University
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.
Prof. Dvir explains: “Our technology is based on taking a small biopsy of belly fat tissue from the patient. 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.
“From the extracellular matrix we produced a personalized hydrogel, that would evoke no immune response or rejection after implantation. We then encapsulated the stem cells in the hydrogel and in a process that mimics the embryonic development of the spinal cord we turned the cells into 3D implants of neuronal networks containing motor neurons.”
The human spinal cord implants were then implanted in lab models, divided into two groups: those who had only recently been paralyzed (the acute model) and those who had been paralyzed for a long time – equivalent to a year in human terms (the chronic model). Following the implantation, 100% of the lab models with acute paralysis and 80% of those with chronic paralysis regained their ability to walk.
Prof. Dvir: “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.
“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. 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.
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.”
Regenerating the injured spinal cord at the chronic phase by engineered iPSCsderived 3D neuronal networks
Cell therapy using induced pluripotent stem cell-derived neurons is considered a promising approach to regenerate the injured spinal cord (SC).
However, the scar formed at the chronic phase is not a permissive microenvironment for cell or biomaterial engraftment or for tissue assembly. Engineering of a functional human neuronal network is now reported by mimicking the embryonic development of the SC in a 3D dynamic biomaterial-based microenvironment.
Throughout the in vitro cultivation stage, the system’s components have a synergistic effect, providing appropriate cues for SC neurogenesis. While the initial biomaterial supported efficient cell differentiation in 3D, the cells remodeled it to provide an inductive microenvironment for the assembly of functional SC implants.
The engineered tissues are characterized for morphology and function, and their therapeutic potential is investigated, revealing improved structural and functional outcomes after acute and chronic SC injuries. Such technology is envisioned to be translated to the clinic to rewire human injured SC.