As illustrated by today's research materials, the state of the art in spinal cord regeneration is improving. Scientists have produce engineered implants consisting of stem cells and hydrogel scaffold material intended to provide an environment conducive to nerve regeneration, and the results in mice are promising. Considered at the high level, this sort of work on implanted scaffolds containing a mix of cell types has been going on for two decades or more. The important advances are all in the details, building the right sort of environment of cells, cell signaling, and supporting metabolites.
All mammals are in principle capable of regenerating nerves. Those nerves were, after all, constructed during early life and then later maintained. Unfortunately adult mammalian tissues have suppressed much of the regeneration that can take place in a developing embryo or very young child. Researchers in the field of regenerative medicine are thus attempting to find the points of control and regulation that will bypass that suppression, allowing cells in injured nerve tissue to act as they did during development. The results here seem an important step in that direction.
Researchers have engineered 3D human spinal cord tissues and implanted them in an animal 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. 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."
The human spinal cord implants were then implanted in two different groups of animal 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 animals with acute paralysis and 80% of those with chronic paralysis regained their ability to walk. Encouragingly, the model animals underwent a rapid rehabilitation process, at the end of which they could walk quite well.
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.