Home » Healing from within: an alternative for the regeneration of the spinal cordIn 2021, according to the National Hospital for Paraplegics (Toledo) and the Institut Guttmann (Barcelona), 915 patients from different Spanish towns received the same news: they had suffered a spinal cord injury.Of course, the causes of this injury were not the same for everyone.In some people the injury was due to trauma, mainly caused by a traffic accident or accidental fall.Others, however, had to assume that the disease they were going through (in some cases cancer, in others a degenerative disease) had also caused damage to their spinal cord.The prognosis of the injury would not be the same for all patients: some would walk out of the hospital under their own power and others would have to undergo rehabilitation.Other people would lose feeling in their limbs, while some patients would never walk again.In February of this year, shocking news broke, on this occasion, in the scientific community: a team of scientists and clinicians led by a French neuroscientist had managed to get three people who had lost complete mobility of the trunk and lower extremities of their body stand up and be able to walk, swim and ride a bike for a few metres.The patients had their spinal cord completely severed due to a motorcycle accident.By implanting 16 electrodes directly on the spinal cord, Grégoire Courtine's team had restored mobility to these people.But that kind of happy ending is rarely fulfilled in patients suffering from severe spinal cord injury.The team from the École Polytechnique Fédérale de Lausanne (Switzerland) chose the subjects of their study very well: young men, with healthy habits and good physical condition.In addition, to regain mobility, the three underwent drug therapy and rehabilitation sessions for months.Courtine's progress offered a hopeful horizon, but certain spinal cord injuries remain incurable today.For this reason, and to face a challenge of these characteristics, it is necessary for science to employ a multidisciplinary strategy, a lesson that the Madrid Institute of Materials Science (ICMM-CSIC) has learned well.Within this CSIC center, physicists, chemists and biologists belonging to the MAG4Spinal project work together to devise a new therapy capable of regenerating damaged tissues in the spinal cord.The spinal cord, together with the peripheral nerves that arise from it, constitutes the most extensive nervous tissue within the human body.From the brain to almost the end of the spine, the axons carry electrical impulses from the brain to the rest of our body, also acting as an orchestra conductor capable of moderating movement and the body's response to external agents like heat or pain.“Many people think that the spinal cord is the tube through which nerves pass from top to bottom.That is an overly simplistic view!The spinal cord is a continuation of the brain, responsible for carrying out the management of all the elements found in the trunk, the extremities and the organs located within the thoracic and abdominal cavities.It therefore has the capacity for autonomous management, although the brain supervises all its actions”, explains Concepción Serrano, a researcher at the ICMM-CSIC.The scientist, a biologist by training, has spent years searching for treatments for different injuries, such as those that occur in vascular and bone tissues.Currently, she is trying to find new therapies to treat spinal cord injuries.Quite a challenge, she comments, due to the very peculiar characteristics that define the central nervous system (CNS): “The regenerative capacity of this system is quite limited due to its high complexity and specialization.It is essential, therefore, to protect it and that is why there are blood-brain and blood-marrow barriers, which are very selective.These barriers protect the CNS from harmful stimuli, but they also make it difficult for good things, for example, drugs, to reach their target in an easy way.”To all this, another factor is added, according to the biologist, and that is that we still do not know 100% how it works: “There are great unknowns regarding certain brain processes, so that wanting to repair something that we still do not understand about the everything becomes a complicated objective”.When I ask Serrano what spinal cord injuries are, the researcher smiles and nods: “It is good that you mention it in the plural, because in fact spinal cord injury does not exist as a single pathology.In reality, each patient has practically a unique spinal cord injury”.Personalized medicine, characterized by the design of therapies and treatments adapted to the needs of each patient, becomes almost a necessity in the case of spinal cord injuries.According to Serrano, the type of injury varies depending on several factors.Damage may occur that only affects the sensory capacity of the person or the mobility of certain limbs may be lost depending on the height at which the injury occurred.In some cases, the patient loses both motor and sensory abilities.In addition, the researcher summarizes, the damage may have been caused by contusions, lacerations (where the spinal cord is severed) or massive compressions.The patient's prognosis will depend on all this, but there is also a component related to their general health: "Most patients who show a good prognosis have little personal history, that is, they are people without previous pathologies who lead a healthy life, with good nutrition and physical activity and who are also young, with which their body has a greater regenerative capacity”.Together with Serrano, other ICMM-CSIC scientists have launched to design a therapy capable of repairing damaged tissues in a spinal cord injury within MAG4Spinal, a National Plan project.Proposal?Use a biocompatible material loaded with different elements that promote the regeneration of the injured area.“Natural hydrogels are ideal biomaterials from the point of view of tissue engineering.They are made up of elements that are already in our body!” says Serrano.When speaking of hydrogels, the biologist refers to materials composed of polymers, groups of molecules that make up an elastic three-dimensional network with many applications in medicine.They have an appearance similar to that of gelatin and their porosity varies depending on the use they are going to have.In recent years, natural hydrogels have caught the attention of many scientists due to their compatibility with the human body.Collagen, hyaluronic acid, chitosan, gelatin... are some of the ideas that Concepción Serrano's group explores in order to find the most compatible hydrogel with the spinal cord.However, this material alone is not capable of activating regeneration in the damaged region;hence the ICMM-CSIC researchers have resorted to the use of iron oxide nanoparticles, tiny particles that, through magnetic stimulation with a magnet placed on the skin, can induce neural regeneration in the damaged area.María del Puerto Morales and Sabino Veintemillas have spent a lifetime as researchers perfecting their technique to produce these particles.“Iron oxide nanoparticles have unique magnetic properties.Also, being so small they can reach everywhere.They have a large surface area, they catalyze many reactions, they are very non-toxic and they are capable of transporting drugs”, sums up Veintemillas.The advantage of using this material, Morales adds, is that it is very cheap to produce and highly biocompatible: “We know how to manipulate it inside our body;we are introducing an element that is not strange to it and that, in fact, is even beneficial in certain quantities”.Although nanoparticles can transport drugs, what these chemists seek in their collaboration with Serrano is to incorporate so-called biological messengers, substances that are naturally found in our body and that play a key role in cell regeneration.Specifically, the nanoparticles will carry nucleic acids."Generally, this genetic component would not enter neurons, which is why we need to use nanoparticles as a vehicle," explains Morales.“Our idea is to use a biocompatible hydrogel loaded with these nanoparticles.By applying an external magnetic field we will heat the surroundings of the nanoparticles, causing the hydrogel to dissolve and allowing them to migrate towards the neurons and penetrate their interior carrying the regeneration mediators”, the scientists explain.In addition, because these particles are magnetic, by applying magnetic fields of controlled direction, scientists can "drag" the nanoparticles in the direction they want, and thus motivate the growth of neurons in the direction that most interests depending on the injury.For the moment, this alliance between researchers has managed to design the nanoparticles and the hydrogel that will carry them.However, they comment, for their therapy to be effective, it is first necessary to understand how both elements behave together.To do this they have the help of Ricardo García's team, a physicist also at the ICMM-CSIC and one of the greatest experts in atomic force microscopy.“A microscope of this type interacts with the sample that we want to study through mechanical processes -says García-.As an analogy we can say that it works like touch.The microscope uses a finger to examine the sample just like we would with our hands, only in this case it's molecular in size."The microscope that García designs and uses measures the interaction between the molecular finger and the atoms, molecules, or surface structures that he wishes to study.Thanks to this technology, the researcher can see changes in the roughness, composition and mechanical properties of the sample, aspects that provide a lot of information about the nature of what he studies.“In the case of biomedical applications, studying these mechanical aspects is highly relevant, since the growth and functioning of cells depend on the mechanical properties of their environment”, explains García.His experience with the atomic force microscope will help the Serrano, Puerto and Veintemillas team to understand how the nanoparticles behave once they are incorporated into the hydrogel, ensuring that they fulfill their function and promote the regeneration of the injured bone marrow.Added to the efforts of the scientists at this CSIC center is the collaboration of the National Hospital for Paraplegics, a leading center in the treatment and rehabilitation of patients with spinal cord injuries.Elisa López-Dolado, a rehabilitation physician, has been working in the field of pediatric spinal cord injuries for years.Her collaboration with Serrano dates back to her formative years as a researcher.“Although our profiles are very different, we found a way to fit both visions.Since then we have worked together”, explains López-Dolado.Her motivation to carry out basic research in spinal cord injuries, she comments, lies in the contact that she maintains on a daily basis with patients whom she cannot cure.One of the strengths of the project, as all its participants attest, is that it incorporates the much-needed conversation between the design of a medical treatment from a basic perspective and its future application as a therapy in real patients.The translation of basic research to clinical application is not a direct or simple path, explains López-Dolado."We need this translation to have a double meaning: for the basic researcher to acquire the ability to communicate with clinical staff and for clinicians to effectively understand what researchers are proposing to us."Within MAG4Spinal, the National Hospital for Paraplegics will be in charge of inserting the hydrogel into lesions made in a rat animal model, and supporting the regeneration of the spinal cord with "regenerative rehabilitation" sessions, designed to activate weakened or lost motor functions after the injury.The collaboration between these scientists did not begin with the National Plan project, which began in 2021, nor will it end when it ends.For years they have tried to find different solutions to face an injury that in many cases completely alters the lives of patients.Together they have faced this challenge thanks to discipline, cooperation and creativity.All of them are aware of the long road ahead of them.At the moment, they continue to work on the frontier of knowledge.We remind you that HEALTH A DAILY is a communication medium that disseminates information of a general nature related to different socio-health areas, so WE DO NOT RESPOND to specific queries about particular medical or healthcare cases.The news we publish does not replace the information, diagnosis and/or treatment or recommendations THAT A HEALTHCARE PROFESSIONAL SHOULD PROVIDE in a given healthcare situation.SALUD A DIARIO reserves the right not to publish or delete all those comments contrary to Spanish law or that are insulting, as well as those that violate 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