Scientists from ETH Zurich in Switzerland have announced a series of successful experiments involving the repair of injured spinal cords in zebrafish and mice after being injected with magnetically controlled microrobots containing pluripotent stem cells.
According to a statement announcing the ETH team’s work, both the zebrafish and mice injected with the microrobots showed improved movement and normalized exploratory behavior within just a few days after treatment.
Although the initial studies were confined to lab animals, the team hopes their magnetically controlled microrobot approach to the precision delivery of pluripotent stem cells could eventually be adapted for humans with spinal cord injuries.
Spinal Cord Repair Microrobots Treat Nerve Cells That Resist Regeneration
Unlike some cells in the human body, nerve cells within the spinal cord rarely regenerate on their own. If the spinal cord is injured, scarring can further reduce the ability of the nerve fibers within the cord to regrow. For people living with spinal cord injuries, this scenario can offer a bleak prognosis for recovery.
In recent decades, scientists have turned to the natural regenerative properties of pluripotent stem cells. Although the use of stem cells was initially controversial due to the need to extract neonatal stem cells, scientists ultimately learned to convert ordinary stem cells into pluripotent stem cells capable of becoming any cell type in the human body.
The most promising approach involves implanting stem cells at the site of the injury and then using electrical stimulation to promote the growth of new cells. However, according to the ETH team behind the new approach, the current method has several drawbacks.
First, stimulating the cells requires the use of implanted electrodes. Second, the team notes that after transplantation, many of the stem cells “do not always survive or integrate properly into the existing tissue.”
To improve healing and increase the chance of restoring spinal cord nerve cell function, they said their new approach combines therapeutic stem cells with magnetoelectric nanoparticles and uses magnetic fields to guide them to the “precise site of an injury” and “stimulate the stem cells to accelerate repair.”
NPCbots Combine Stem Cells and Magnetically Controlled Nanoparticles
To construct their magnetically guided spinal cord repairing robot, the team built what they termed a “biohybrid microrobot.”
First, the team creates pluripotent stem cells from adult cells by genetically manipulating them in the lab. The result is what researchers call an “induced” pluripotent stem cell (iPS). According to the study authors, these newly pluripotent iPS cells are used to derive living neural progenitor cells (NPCs), meaning “they have the potential to differentiate into various types of nervous system cells.”
Next, the team creates customized magnetic nanoparticles consisting of two layers. The inner layer responds to the “commands” from the magnetic fields used to control them, and an outer layer that converts this response into an electrical signal.
According to Professor Salvador Pané i Vidal of the Multi-Scale Robotics Lab at ETH Zurich, each tiny robot has a reservoir near the center “where we trap the cells.” The professor said the best way to accomplish this is to inject the nanoparticles into a solution with the NPC, “and wait for the two components to bind.”
After 30 minutes, the process is complete, and the team is left with a batch of nanobots, each around 6 micrometers in size. Since the new robots combine a magnetic bot and a reservoir of NPCs, the team named them ‘NPCbots.’
In preparatory cellular experiments, the researchers used hundreds of thousands of NPCbots. However, several million were required for animal trials.
Zebrafish and Mice Regain Movement After Injections
To test the efficacy of their new NPCbots, the ETH team injected millions of them into the spinal cord of zebrafish larvae with spinal cord injuries. To improve the chances of nerve regeneration, the NPCbots were injected directly into the site of the injury.
After injecting the microrobots, the injury site was subjected to electromagnetic fields. Although the repair was not immediately evident, the team noted that after three days, the zebrafish with the injured spinal cords “exhibited nearly normal swimming and exploratory behaviour.”
Next, the team injected millions of NPCbots into mice with completely separated spinal cords. According to the team, the results were “very promising.”
“After 28 days, the animals’ nerve cells had reconnected at the site of the injury,” they explained.
The team said further observation of the treated mice revealed “increasingly normal movement patterns,” including improvements in gait, stride length, and coordination. The ETH team also noted that the mice’s exploratory behavior “improved significantly.”
When discussing the mouse experiments, the team described the result as “particularly significant” because zebrafish spinal cords regenerate, whereas mouse spinal cords do not. They also noted that the treatment was “well tolerated by the animals,” with no reported immune reactions or adverse effects.
Minimally Invasive and More Precise Treatments with Microbots
Unlike science fiction movies, where tiny robots repair tissue mechanically, the research team said that the stem cells carried by the NPCbots are exposed to electrical stimulation, “greatly enhancing their differentiation after transplantation.” This means the nanoparticles convert the electric signals from the EM field into electrical impulses, stimulating healing.
Unlike more complicated stem cell procedures that use implanted electrodes and cables, the team said they only needed to apply external magnetic fields around the spinal cord injury site. The team said this simplification was “crucial,” since the spinal cord is considered extremely sensitive. They also note that the ability to manipulate the frequency and field strength of magnetic fields, combined with their ability to penetrate deeply into tissue, makes the entire process safe and easy to control.
“Microrobotic guidance makes the treatment more precise and minimally invasive,” Hao explained.
After the NPC bots have delivered and stimulated the stem cells, the team said they “essentially dissolve” within the tissue. Because the bots contain a barium titanate coating, the researchers also believe that they will be “stable and minimally reactive” with surrounding tissue. Still, they concede that “further studies will determine whether and how the particles are degraded or excreted over the long term.”
Expanding NPCbot Therapies to Increase the Effectiveness of Other Targeted Therapies
Although the team described the animal trials of their NPCbots as “promising,” they noted that further research is needed before the process can be attempted on human patients with spinal cord injuries. For example, Hao noted that in addition to ‘clinical aspects’ that require more exploration, the team needs to start by determining which magnetic fields “work best in humans” and determining the “optimal stimulation duration” for human NPCs. Nevertheless, the team noted, they are “already considering further applications.”
“The reproducible and scalable production of microrobots using our lab-on-a-chip system demonstrates that the platform’s application potential extends beyond basic research,” Professor Vidal explained.
Some potential biomedical applications mentioned by the RETH team include cardiology, oncology, wound healing, “and other targeted therapies,” adding that their process could make such treatments “safer, more controllable and more effective.”
The study “Magnetoelectric Microrobots for Spinal Cord Injury Regeneration” was published in Nature Materials.
Christopher Plain is a Science Fiction and Fantasy novelist and Head Science Writer at The Debrief. Follow and connect with him on X, learn about his books at plainfiction.com, or email him directly at christopher@thedebrief.org.