A million-person study points to repeated heat injury in the oesophagus.Paleontologists studying a fossil unearthed in southern Manitoba, Canada, have identified what they believe are two bite marks on the internal skeleton of the ancient giant cephalopod Enchoteuthis.
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The Marcus Foundation has awarded $28.7 million to Chuck Murry, MD, PhD, director of the USC Stem Cell Center, to support a clinical trial testing a stem cell-based therapy intended to regenerate heart muscle damaged by a severe heart attack. The award, the largest the foundation has given to the University of Southern California and one of its largest contributions to academic medicine, will fund both the planned human study and a parallel research program examining how the immune system responds to transplanted cardiac cells.
The trial is scheduled to begin in 2027 at Keck Hospital of USC in partnership with the USC Cardiac and Vascular Institute. A second clinical site will be established at the University of Washington, where elements of the technology were originally developed. The first phase will enroll approximately 18 patients who have experienced extensive myocardial infarction, the medical term for a heart attack that destroys part of the heart’s muscular wall.
Patients in the study will receive stem-cell-derived heart muscle cells delivered into regions damaged by the infarction. The primary goals will be to evaluate safety and determine whether the procedure is feasible in people with severe cardiac injury. Investigators will also monitor early biological signals, including whether the transplanted cells remain active, integrate with the injured tissue and produce measurable changes in cardiac performance during recovery and long-term follow-up.
A heart attack occurs when blood flow through a coronary artery is blocked, depriving cardiac muscle of oxygen. Within minutes, cells in the affected region begin to die, and the resulting scar tissue lacks the contractile properties of healthy myocardium. Unlike tissues such as skin or blood, adult human heart muscle has only a limited capacity for self-repair. As a result, a large infarction can weaken the heart’s pumping function, increase the risk of heart failure and leave survivors unable to perform ordinary activities without fatigue or breathlessness.
Current cardiovascular treatments can reopen blocked arteries, limit further injury and help the remaining heart muscle work more efficiently. They cannot, however, routinely replace the cardiomyocytes that have already been lost. Murry’s research program is aimed at addressing that biological gap by producing replacement heart muscle cells in the laboratory and delivering them directly to damaged tissue. The strategy represents a shift from supporting a failing heart to attempting to rebuild part of its contractile apparatus.
The transplanted cells are being developed as a form of cellular therapy, in which living cells act as the therapeutic agent rather than serving merely as a vehicle for a drug. According to Murry, the cells are intended to become active within the injured heart, contribute to repair and synchronize with surrounding muscle. Achieving that outcome requires more than placing new cells into scarred tissue: the cells must survive, connect functionally with the host myocardium and avoid creating dangerous electrical disturbances or abnormal rhythms. The initial trial is therefore designed principally to establish safety before testing therapeutic effectiveness in larger patient groups.
The foundation’s funding will also support research into the immune response triggered by cell transplantation. Even cells created from stem cells can be recognized as foreign by the recipient’s immune system, potentially leading to inflammation or destruction of the transplanted population. Patients who receive cellular grafts may consequently require immunosuppressive drugs, which can increase susceptibility to infection and produce other long-term complications. Researchers will study how immune cells interact with the implanted cardiac cells and investigate methods that could reduce or eventually eliminate the need for chronic immunosuppression.
The work builds on approximately three decades of research by Murry and his collaborators to move regenerative cardiology from laboratory experiments toward clinical treatment. The program includes gene-edited cellular technology, intended to improve the compatibility or performance of therapeutic cells in the human body. The precise effectiveness of the approach will not be known until it is tested in patients, and the small 2027 cohort will not be large enough to determine whether the therapy improves survival or prevents heart failure. Those questions would require subsequent trials involving substantially more participants and longer observation.
The Marcus Foundation described the project as a potential turning point for regenerative medicine, while USC leaders said the investment could create a platform for developing additional cellular therapies. The immediate scientific challenge is to determine whether transplanted heart muscle cells can be delivered safely and function meaningfully within severely damaged human hearts. If the trial meets its safety and feasibility objectives, it could provide the clinical evidence needed to advance a new generation of treatments for myocardial infarction—therapies designed not only to help patients live with damaged cardiac tissue, but to restore some of the function that conventional medicine cannot yet replace.
Subject of Research: Stem cell-based regenerative therapy for heart muscle damaged by myocardial infarction
Article Title: $28.7 Million Award Supports USC Trial of Stem Cell Therapy to Regenerate Heart Muscle After Heart Attack
Web References: The Marcus Foundation: https://marcusfoundation.org/; USC Stem Cell Center: https://stemcell.keck.usc.edu/; Chuck Murry Lab: https://murrylab.usc.edu/charles-chuck-murry-md-phd/; USC Cardiac and Vascular Institute: https://www.keckmedicine.org/services/cardiovascular/; Keck School of Medicine of USC: https://keck.usc.edu/
Image Credits: Steve Cohn
Keywords: Heart disease, myocardial infarction, heart attack, heart muscle, stem cell research, stem cell therapy, cell therapy, regenerative medicine, cardiovascular disorders, heart failure, clinical trial, cardiac regeneration
Spinal cord injury (SCI) represents one of the most devastating neurological conditions, profoundly disrupting sensory, motor, and autonomic functions below the level of injury. Its consequences extend far beyond mere physical impairment, encompassing a complex web of psychological and social challenges that pose a substantial burden on patients and their caregivers. Among the myriad complications that arise following SCI, the loss of voluntary control over bladder function remains particularly debilitating, undermining patient autonomy, quality of life, and dignity. The intricate interplay of neural pathways governing lower urinary tract function becomes severely compromised, leading to neurogenic bladder dysfunction that is intricately linked with heightened risks of urinary tract infections, renal damage, and incontinence.
For decades, researchers have relied extensively on animal models to unravel the pathophysiological underpinnings of SCI and its associated comorbidities. These preclinical platforms have proven indispensable in dissecting the cellular and molecular cascades triggered by spinal trauma, enabling the identification of potential therapeutic targets. Through controlled experimental conditions, scientists have been able to mimic various types of SCI lesions, from contusions to complete transections, affording nuanced insights into injury severity and plasticity mechanisms. Moreover, animal models facilitate the rigorous testing of novel interventions — ranging from pharmacological agents to neuromodulatory devices — that aim to restore neural circuits or promote regeneration within the damaged spinal cord.
Despite these advancements and the critical role that animal experimentation has played, a persistent and contentious debate surrounds the translational effectiveness of these models. The stark reality is that many promising therapeutic strategies that yielded encouraging results in animals have failed to replicate similar benefits in human clinical trials. This translational gap underscores the biological and physiological differences between species, as well as the complexity of accurately reproducing the heterogeneity and chronicity of human SCI in simpler model organisms. Ethical considerations also compound the urgency for innovation, fueling a global momentum toward reducing reliance on animal studies where feasible and developing alternative methodological approaches.
In the evolving landscape of biomedical research, technological progress is fostering the emergence of cutting-edge in vitro and in silico models that promise to complement or potentially supplant traditional animal-based experiments. Organoids, microfluidic systems, and advanced computational simulations are gaining traction as sophisticated tools capable of recapitulating key elements of spinal cord architecture and function. These platforms aspire not only to reduce animal use but also to offer greater experimental control and reproducibility, potentially accelerating the pipeline from bench to bedside. Importantly, regulatory agencies are increasingly acknowledging and supporting these innovative approaches, embedding them within frameworks that ensure safety and efficacy without compromising ethical standards.
A nuanced understanding of neuro-urological dysfunction post-SCI exemplifies the complexity of this translational challenge. The control of bladder function is regulated by an intricate network involving supraspinal centers, spinal interneurons, and peripheral autonomic pathways. Following SCI, this orchestration is disrupted, with varying patterns of dysfunction depending on the lesion level and severity. Animal models, ranging from rodents to large mammals, capture distinct aspects of these patterns and have been pivotal in characterizing mechanisms like detrusor overactivity, sphincter dyssynergia, and altered afferent signaling. However, clinical phenotypes observed in humans often present additional layers of intricacy that are not fully paralleled in animal studies, highlighting the necessity for enhanced model fidelity.
Within experimental contexts, the choice of animal species and injury paradigms is driven by the specific research question being addressed. Rodents, primarily rats and mice, are favored for their genetic tractability, well-established behavioral assays, and cost-effectiveness. Larger mammalian models such as cats, dogs, and non-human primates offer advantages in anatomical and physiological similarity to humans but involve substantial ethical and logistical challenges. Each model carries inherent limitations in terms of reproducing chronic injury states, co-morbid conditions, and the psychosocial dimensions of SCI, factors that have contributed to translational discrepancies in therapeutic development.
Advances in imaging technologies, electrophysiological monitoring, and biomarker identification have supplemented animal research by enabling more precise phenotyping of SCI and its neuro-urological consequences. Functional MRI, calcium imaging, and optogenetics provide unprecedented views into spinal cord circuitry and its plastic adaptations, facilitating the assessment of intervention efficacy at multiple neurobiological scales. Nonetheless, integrating these sophisticated methods across species and in translational studies demands rigorous standardization and validation to ensure data comparability and clinical relevance.
Contemporary therapeutic strategies emerging from animal research encompass pharmacological modulators targeting neurotransmitter systems, stem cell transplantation to replace lost or damaged neurons, and bioengineering approaches aimed at bridging lesion gaps or providing scaffolding for axonal regrowth. Neuromodulation techniques such as electrical stimulation of sacral nerves or the spinal cord itself have shown promise in restoring partial bladder control, with a handful of such technologies transitioning into clinical trials. These advances underscore the indispensable role of preclinical models in pioneering interventions that address both the neurogenic bladder and the broader spectrum of SCI-induced disability.
Looking ahead, the field stands at a crossroads, poised between longstanding reliance on animal experimentation and the transformative potential of emerging modeling strategies. While animal models remain critical for certain studies, the integration of alternative approaches is anticipated to accelerate in the coming decade. Such a paradigm shift will depend not only on technological innovations but also on a collaborative ecosystem involving scientists, clinicians, regulatory bodies, and patient advocacy groups to harmonize research priorities and ethical considerations.
Indeed, the question of whether animal models will retain their central role in neuro-urological SCI research by 2035 reflects broader themes in biomedical research ethics, experimental rigor, and translational success. A hybridized methodology that combines animal models with advanced in vitro systems and computational models may offer the most fruitful path forward, marrying the biological relevance of whole organisms with the precision and scalability of engineered platforms. This integrative approach could foster more effective therapies for SCI patients suffering from bladder dysfunction, reducing the human and economic toll of this challenging condition.
Crucially, patient-centered outcomes must guide research priorities, ensuring that innovations translate into tangible improvements in bladder control, autonomy, and quality of life. The intersection of neurobiology and urology demands interdisciplinary collaboration and sustained investment in technologies that can simulate the complex neurogenic bladder environment. Such efforts will define the scientific landscape of SCI research, promising new horizons in repair and rehabilitation.
Regulatory frameworks will also play a pivotal role in steering the future of SCI research methodologies. Agencies are increasingly promoting the 3Rs principle—replacement, reduction, and refinement of animal use—with heightened scrutiny on the predictive validity of animal models. Enhanced guidelines supporting alternative models could incentivize their adoption and facilitate expedited regulatory approval for novel therapeutics. This dynamic will likely reshape both academic and industry research strategies in neuro-urology.
In sum, while animal models have undeniably been cornerstones of SCI neuro-urological research, the field is undergoing a fundamental transformation informed by ethical imperatives, scientific rigour, and technological innovation. The trajectory toward 2035 suggests a diminishing but not extinguished role for animal experimentation, coexisting with advances that enhance the resolution and relevance of preclinical research. This evolution holds promise to one day liberate SCI patients from the grip of neurogenic bladder dysfunction, restoring dignity and function through precision medicine grounded in robust scientific inquiry.
The road ahead is both challenging and exhilarating, promising breakthroughs borne from an unprecedented synergy of traditional biological models and revolutionary engineering and computational tools. As neuroscience and urology converge on the frontier of spinal cord repair, the legacy of animal research endures—not as a relic but as a foundational pillar supporting the ascent toward a future where SCI is a treatable rather than a life-altering diagnosis.
Subject of Research: Animal models of spinal cord injury in neuro-urological research
Article Title: Animal models of spinal cord injury in neuro-urological research
Article References:
Giannotti, A., Aguinaga, D.M., Ferreira, A. et al. Animal models of spinal cord injury in neuro-urological research. Nat Rev Urol (2026). https://doi.org/10.1038/s41585-026-01163-6
Image Credits: AI Generated
Microplastics: Unseen Threats to Liver Health Revealed Through Cutting-Edge Spatial Transcriptomics
In recent years, microplastics have emerged as pervasive environmental contaminants, infiltrating virtually every corner of the globe. These minuscule plastic particles, derived from the breakdown of larger plastic debris, have invaded air, water, and soil, exposing humans to continuous contact via inhalation, ingestion, and dermal absorption. Despite the ubiquity of microplastics, understanding their direct impact on biological systems has remained a formidable challenge within the scientific community. A groundbreaking study by researchers at the University of Oklahoma, recently published in the journal Science Advances, delves into this critical area by examining how microplastics particularly affect liver health under dietary stress conditions.
Tae Gyu Oh, Ph.D., an assistant professor of oncology science at the University of Oklahoma College of Medicine and lead author of the study, highlights the pressing concern: “Exposure to microplastics is inevitable. Their presence in human tissues has been confirmed across multiple studies. However, we wanted to investigate how microplastic exposure interacts with a high-fat, high-cholesterol diet, known to independently induce liver damage.” The study offers compelling evidence that the combination of a typical Western diet and microplastic exposure exacerbates liver injury, potentially accelerating the progression of metabolic liver diseases.
Central to the study is the focus on polyethylene, the most prevalent plastic polymer globally, commonly found in everyday items such as plastic bags and milk containers. The research team administered polyethylene microplastics to mice over eight weeks, with one cohort receiving a standard diet and another subjected to a diet mimicking metabolic dysfunction-associated steatohepatitis (MASH). This severe form of fatty liver disease is characterized by inflammation and liver cell damage, often culminating in cirrhosis and liver failure if untreated.
The findings were striking: mice consuming the high-fat diet alongside microplastic exposure exhibited blood markers indicating liver injury more than twice as elevated as those on a standard diet experiencing similar exposure. This synergistic effect underscores the intricate interplay between environmental pollutants and diet-induced metabolic stressors, intensifying hepatic damage beyond what each factor causes independently.
To unravel the molecular and cellular underpinnings of this phenomenon, the research employed an array of sophisticated analytical techniques, culminating in the use of spatial transcriptomics. Unlike conventional bulk transcriptomic approaches, which average gene expression across millions of cells and can obscure localized responses, spatial transcriptomics enables researchers to map transcriptional activity within intact tissue sections at near single-cell resolution. This technique revealed precise “hot spots” of inflammation and tissue injury within the liver, a breakthrough insight unattainable by earlier methodologies.
Analysis of gene regulatory networks through spatial transcriptomics indicated a pivotal role for PPAR-alpha (peroxisome proliferator-activated receptor-alpha), a nuclear receptor that orchestrates fat metabolism and energy homeostasis in liver cells. PPAR-alpha appears to engage in cross-talk with Anxa2, a gene implicated in tissue repair and membrane dynamics. The altered activity of this axis in microplastic-exposed livers suggests that microplastics may disrupt the liver’s natural defense and regenerative processes, impairing its capacity to recover from metabolic insults.
This discovery has profound implications for understanding the mechanistic pathways by which environmental contaminants like microplastics contribute to liver pathology. The perturbation of PPAR-alpha and Anxa2 signaling potentially links microplastic exposure with the dysregulation of lipid metabolism and compromised repair, exacerbating the severity of conditions such as nonalcoholic fatty liver disease (NAFLD) and MASH.
While these findings were generated in a murine model, they establish an essential framework that informs potential human health risks. Given the parallels between murine and human liver physiology, it is plausible that microplastic exposure combined with high-fat diets could similarly predispose humans to aggravated liver damage. However, the researchers caution that further studies are necessary to confirm this translation and to elucidate the long-term implications for populations worldwide.
Dr. Oh emphasizes the broader relevance of this research: “Microplastics are now inextricably linked to daily life, yet their biological impact is only beginning to be understood. Through advanced spatial transcriptomic mapping, we have visualized the precise loci of hepatic damage induced by microplastics, revealing a novel environmental dimension to liver disease pathogenesis.” This nuanced comprehension paves the way for future investigations targeting environmental and dietary risk factors in liver health.
Moreover, these insights open avenues for therapeutic targeting. Modulating the PPAR-alpha-Anxa2 pathway could become a strategy to mitigate microplastic-induced liver injury or fortify the liver’s resilience against environmental toxins. Understanding such molecular crosstalk also facilitates improved diagnostic markers sensitive to environmental damage, allowing for earlier intervention in vulnerable populations.
This pioneering study exemplifies the intersection of environmental health, genomics, and hepatology, demonstrating how innovative technologies can elucidate complex biological interactions. It underscores the urgent need to address microplastic pollution not only as an ecological crisis but as a public health priority, particularly in societies where high-fat diets are prevalent.
As humanity grapples with escalating plastic waste and its fragmentary descent into invisible pollutants, research such as this serves as a clarion call for comprehensive strategies. Reducing plastic production, enhancing waste management, and fostering healthier dietary practices collectively form the cornerstone of mitigating hidden dangers to liver health and overall well-being.
The University of Oklahoma study, titled “Spatial Transcriptome Mapping Identifies Ppara-Anxa2 Crosstalk in Microplastic-Induced Hepatotoxicity,” stands as a seminal contribution offering unprecedented mechanistic clarity. Through employing spatial transcriptomics, the researchers have achieved a level of resolution that redefines how environmental toxicology and metabolic disease research can coalesce to confront emergent health threats posed by our plastic-saturated environment.
Subject of Research: Animals
Article Title: Spatial transcriptome mapping identifies Ppara-Anxa2 cross-talk in microplastic-induced hepatotoxicity
News Publication Date: 17-Jun-2026
Web References: https://doi.org/10.1126/sciadv.aec8681
References: Oh, T.G., Jung, W., Joshi, A.D., et al. Spatial Transcriptome Mapping Identifies Ppara-Anxa2 Crosstalk in Microplastic-Induced Hepatotoxicity. Science Advances, 2026.
Image Credits: University of Oklahoma
Keywords: Microplastics, Liver Disease, Fatty Liver Disease, Polyethylene, High-Fat Diets, Spatial Transcriptomics, PPAR-alpha, Anxa2, Hepatotoxicity, Environmental Health, Metabolic Dysfunction, Inflammation
A groundbreaking discovery at the University of California, Los Angeles (UCLA) has unveiled a promising new therapeutic avenue for kidney regeneration, leveraging a drug initially designed to repair heart tissue following myocardial infarction. This drug, known as AD-NP1, targets a specific protein—ENPP1—that plays a critical role in impeding the body’s natural healing processes in injured tissues. The revelation that AD-NP1 can also accelerate kidney repair heralds a significant advancement in regenerative medicine, especially for patients suffering from chronic kidney disease (CKD), a condition that affects millions globally.
The heart of this research revolves around a protein named ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). When tissues such as the heart or kidney sustain injury, ENPP1 production escalates, initiating a cascade of metabolic disturbances that hinder energy synthesis within cells. This disruption compromises cellular function and ultimately stalls effective tissue regeneration. In the context of the kidney, which is vital for maintaining systemic homeostasis, such impediments can lead to progressive scarring and functional decline, culminating in kidney failure.
Through years of meticulous experiments, the UCLA team delineated the detrimental impact of ENPP1 on the kidney’s reparative capacity. They observed that injured renal tissue upregulates ENPP1 expression, which in turn resets the metabolic landscape of cells in the damaged microenvironment. This altered metabolic signaling disrupts mitochondrial function, thereby curtailing ATP production essential for cell proliferation and repair. By employing genetic knockout models in mice, where ENPP1 expression was inhibited, the researchers documented a striking enhancement in renal recovery post-injury. These mice demonstrated reduced fibrotic scarring and improved renal biomarkers, signaling restored kidney function.
Central to translating these findings into potential clinical interventions is AD-NP1, a sophisticated monoclonal antibody engineered to specifically neutralize ENPP1. Unlike broad-spectrum immunosuppressants or anti-inflammatory agents, AD-NP1 offers targeted therapeutic precision by binding solely to human ENPP1, circumventing off-target effects. Initially conceptualized to mitigate cardiac fibrosis and promote myocardial regeneration following heart attacks, AD-NP1’s mechanism exerts a similar rejuvenating influence on kidney tissues. The antibody effectively halts the ENPP1-induced metabolic sabotage, facilitating an environment conducive to cellular proliferation and tissue repair.
In experimental paradigms, the administration of AD-NP1 in mice subjected to nephrotoxic diets and chemically induced renal injuries yielded compelling outcomes. Within merely seven days of treatment, subjects exhibited marked improvements in kidney function tests and histological assessments showed diminished collagen deposition and scarring. These findings underscore the drug’s potential to transform the management of acute and chronic kidney injuries by reinstating the organ’s intrinsic regenerative programs, which are often stifled in disease states.
Moreover, the team’s translational approach integrated analyses of human kidney biopsies acquired from individuals with chronic kidney disease. These samples consistently manifested elevated ENPP1 levels relative to healthy controls, substantiating the protein’s pathological role in human renal disorders. This correlation not only reinforces the relevance of the preclinical models used but also paves the way for clinical evaluation of AD-NP1’s efficacy in human subjects suffering from renal ailments.
The broader implications of this discovery extend into the metabolic regulation of tissue repair. ENPP1’s role appears multifaceted, orchestrating cellular energy dynamics and intercellular communication networks that dictate regenerative outcomes. Inhibiting this protein intervenes in maladaptive signaling cascades, thereby restoring bioenergetic balance and enabling clonal expansion of healthy cells adjacent to injury sites. This paradigm shift in understanding organ regeneration emphasizes metabolic modulation as a cornerstone of effective healing strategies.
Prior to this research, the therapeutic targeting of ENPP1 was primarily confined to cardiac medicine. The successful repurposing of AD-NP1 for kidney injury illustrates the concept of cross-organ regenerative mechanisms, where molecular pathways governing tissue healing are conserved albeit contextually modulated. This discovery propels the field into a new frontier, advocating for the exploration of shared regenerative targets that can be manipulated across diverse organ systems.
AD-NP1’s journey into clinical trials commenced recently with FDA approval of a Phase 1 safety study in human patients recovering from heart attacks. This milestone reflects the rigorous preclinical validation of the drug’s pharmacodynamics and safety profile. Building on these milestones, ongoing efforts at UCLA aim to extend these trials to include patients with progressive kidney disease, setting the stage for comprehensive evaluation and potential future clinical application.
Underlying this innovative research are substantial investments from the National Institutes of Health, California Institute of Regenerative Medicine, and the U.S. Department of Defense. This underscores the strategic importance and translational potential of regenerative medicine therapies in addressing chronic diseases that impose heavy societal burdens. The interdisciplinary collaboration among cardiovascular scientists, nephrologists, and molecular biologists at UCLA exemplifies the synergy needed to unlock complex biological processes for therapeutic gain.
In summation, the identification of ENPP1 as a metabolic gatekeeper that impedes tissue repair, combined with the development of AD-NP1 to neutralize its effects, represents a significant leap forward in regenerative medicine. The drug’s ability to foster organ regeneration by restoring metabolic and cellular homeostasis offers hope for millions afflicted by kidney disease and opens novel avenues for organ repair strategies. As clinical trials progress, the scientific community eagerly anticipates further validation of these findings, potentially heralding a new era where molecularly targeted therapies can substantially reverse organ damage and restore quality of life.
Subject of Research: Kidney regeneration, metabolic regulation of tissue repair, ENPP1 protein inhibition, monoclonal antibody therapy
Article Title: UCLA Researchers Discover Novel Role for ENPP1 Inhibition in Enhancing Kidney Repair via AD-NP1
News Publication Date: Not specified (based on provided content)
Web References: Cell Stem Cell Journal Article
Keywords: ENPP1, kidney injury, chronic kidney disease, tissue regeneration, monoclonal antibody, AD-NP1, metabolic signaling, renal repair, fibrosis, UCLA, regenerative medicine, Phase 1 clinical trial
A contraceptive drug helps human nerve cells regenerate by unlocking their forgotten embryonic healing abilities.
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.
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.”
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.
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.
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.”
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.
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