Article In Brief
Mice with an open- and closed-traumatic brain injury were injected with immunomodulatory nanoparticles that reduced brain swelling and damage on MRI.
Investigators used a novel approach to prevent the swelling that can occur after traumatic brain injury (TBI) in a mouse model: they injected nanoparticles that trick white blood cells into going after them instead of rushing to the injured brain and causing an inflammatory and immune response.
Mice with TBI that were given three injections of the immunomodulatory nanoparticles beginning two to three hours after injury showed less brain swelling and damage on MRI as compared with mice with TBI that did not get the nanoparticles; the treated mice also performed better on functional tests.
The immunomodulatory nanoparticle treatment, if further proven in preclinical trials and human trials, would not undo damage from the initial injury to the brain. But it could help prevent the body from setting off a cascade of immune and inflammatory cells in reaction to the injury, which in turn can cause brain swelling and even more damage to brain tissue.
We certainly haven't gone and magically prevented that initial damage, said Jack Kessler, MD, professor of neurology at Northwestern University Feinberg School of Medicine and the senior author of the paper. What we can do is prevent the secondary damage, which is substantial.
Predicting which TBI patients will develop edema of the brain isn't easy, so having a preventive treatment like the nanoparticles that could be administered upfront could be life-altering, Dr. Kessler said.
He said some patients with head injuries come into the hospital walking and talking, but then their brain swells, and they die.
According to background in the study, published January 10 online in Annals of Neurology, each year more than 2.5 million people in the US have a traumatic brain TBI and more than five million Americans live with at least one sequela of TBI.
After the primary injury, there is substantial secondary injury attributable to infiltrating immune cells, cytokine release, reactive oxygen species, excitotoxicity, and other mechanisms, the study authors wrote. Despite many preclinical and clinical trials to limit such secondary damage, no successful therapies have emerged.
The nanoparticles tested in the mouse experiments are made of material used in biodegradable sutures. The paper specifically described the particles as highly negatively charged, 500 nm-diameter particles composed of the Food and Drug Administration (FDA)-approved biodegradable biopolymer carboxylated poly (lactic-co glycolic) acid.
The nanoparticles (IMPs), which seem like foreign invaders to the body's immune system, attract the attention of large white blood cells known as monocytes, which have been implicated in the secondary damage that occurs with TBI.
IMPs bind to the macrophage receptor with collagenous structure (MARCO) on monocytes and monocytes bound to IMPs no longer home to sites of inflammation but rather are sequestered in the spleen, where the cells die, the study authors wrote.
The mouse study involved two types of head injury. In some of the mice, the researchers performed a craniotomy to create a controlled cortical impact. Other mice received a closed head injury involving a direct blow to the head. Both types of injuries were meant to mimic what occurs in humans with TBI.
Injections of the nanoparticles were given two to three hours after the brain injury, and again at 24 hours and 48 hours post-injury. Control animals with similar brain injuries were given saline solution at the same time points.
Outcomes for the mice who received the nanoparticles were better by multiple measures, including MRI and a motor function test called the ladder rung walking test that is used in mouse experiments.
IMP administration resulted in remarkable preservation of both tissue and neurological function, in both models of head injury, the paper said. After acute treatment, there was a reduction in the number of immune cells infiltrating into the brain, mitigation of the inflammatory status of the infiltrating cells, improved electrophysiological visual function, improved long-term motor behavior, reduced edema formation as assessed by magnetic resonance imaging, and reduced lesion volumes on anatomic examination.
Dr. Kessler said that in the case of mice with an open head injury, the size of their brain lesion was 50 percent smaller in the treated animals compared with those that did not get the nanoparticles.
He said MRI showed significantly less brain swelling and less compression of the ventricles, both signs that secondary damage was minimized.
Dr. Kessler said that right now the only recourse for severe brain swelling is to do a craniotomy to relieve pressure in the skull.
He said one of the appeals of the nanoparticle treatment is that an emergency medical technician could do it in the field or the emergency room personnel could inject it.
But Dr. Kessler is also cautious about too many predications based on a pre-clinical study, saying he is fond of telling medical students that if I had a nickel for every mouse we cured, I'd be a rich man.
Sripadh Sharma, PhD, an MD-PhD student at Northwestern and the study's first author, said the nanoparticle therapy needs to be tested further in animal models before it could go into human testing. The researchers also want to learn more about how the nanoparticles bring about a reduced immune response in the body.
Dr. Sharma noted that while immune responses are a good thing in the face of injury or infection, sometimes nature doesn't always get it right, so too much of a good thing is a bad thing. And that can be the case with TBI.
He said it has been shown by another collaborator on the study, Stephen Miller, PhD, that when the scavenger receptors on the monocytes detect the light negative charge of the nanoparticles, the monocytes engulf and bind to the particles and apoptose in the spleen instead of going to the site of injury.
More studies need to be done to optimize what dose and what time these particles need to be given following a head injury, said Dr. Sharma.
Similar nanoparticle therapy is being tested for other medical conditions, including celiac disease and myocardial infarction, Dr. Kessler said.
Michael J. Schneck, MD, FAAN, professor of neurology (and neurosurgery) at Loyola University Chicago, said the study was well-designed and thorough, using two different head injury models and multiple outcome measures, including brain imaging, functional testing, and brain tissue analysis. Dr. Schneck said the paper made him wonder whether a similar approach using immune-modulating nanoparticles could reduce inflammatory-related damage following stroke and spinal cord injury.
Dr. Schneck said the concept of trying to dampen the immune response after TBI to prevent edema is not new, but the Northwestern researchers took the idea in a new direction. The nanoparticle therapy is particularly intriguing, he said, because it is fairly simple and involves the use of a material that is already approved by the US FDA, which could mean that it would take less time to move the therapy from the laboratory into clinical trials.
This is a very elegant study with interesting translational potential, he said. But it is a mouse model and its application to (human) TBI and other forms of central nervous system injury remains to be validated.
Jiangbing Zhou, PhD, associate professor of neurosurgery and biomedical engineering at Yale University, said that as someone who does research in the field of nanomedicine, he was surprised by the study's findings and wants to understand how this simple formulation particle could achieve this marked efficacy.
The study looks very exciting, but I want to know more about the mechanism, said Dr. Zhou, whose research focuses on developing translational nanomedicine, gene therapy, and stem cell therapy for neurological disorders including TBI.
He had these and other questions about the study: Why do the particles interact specifically with the inflammatory monocytes but not the others? How do the particles, which are made of safe biomaterials, efficiently kill the inflammatory monocytes in the spleen? What is happening and why?
Javier Crdenas, MD, director of the Barrow Concussion and Brain Injury Center at the Barrow Neurological Institute, said the study on the immune-modulating nanoparticle therapy for TBI was very promising, though he stressed that he is always cautiously optimistic when he sees a mouse study.
It is definitely a novel approach to addressing the secondary sequelae of brain injury and they might have something that minimizes that and hopefully improves outcomes, Dr. Crdenas said.
He said the study also raises some questions, including how the immune-modulating approach would fare in patients who have multiple injuries, not just to the head.
Dr. Crdenas said brain injuries often do not happen in isolation, with patients also having broken bones, lacerations, and other organ damage.
We don't know how this (nanoparticle treatment) would affect other organs, other immune responses elsewhere in the body, he said.
Dr. Crdenas said the field of TBI research has been disappointed before by studies of new therapies that looked promising in animal models and clinical testing but ultimately failed. He noted, for instance, that progesterone and hypothermia did not turn out to be good at preventing brain swelling.
We will wait and see, he said of the nanoparticles.
Drs. Sharma, Schneck, Zhou, and Crdenas had no disclosures.
More here:
Nanoparticle Therapy Might Help Reduce Brain Swelling in... : Neurology Today - LWW Journals
- The therapeutic potential of stem cells - PMC - December 19th, 2024
- Researchers find success with stem cell therapy in mice model of ... - December 19th, 2024
- Advancing the Battle against Cystic Fibrosis: Stem Cell and Gene ... - December 19th, 2024
- Study finds stem cell therapy is safe and may benefit people with ... - October 22nd, 2024
- Stem Cell Therapy Market Size to Hit USD 48.89 Billion by 2033 - GlobeNewswire - October 22nd, 2024
- Eves dream to walk: Family raising vital funds for two-year-olds stem cell therapy - Her.ie - October 22nd, 2024
- Stem cell therapies for chronic obstructive pulmonary disease ... - September 21st, 2024
- Magellan Stem Cells welcomes $7 million federal government grant - September 21st, 2024
- Stem Cell Therapy Research: Creative Biolabs Advances iPSC-Derived Macrophage Solutions - openPR - September 21st, 2024
- Stem Cell Therapy Market Dynamics: Size, Share, and Growth - openPR - September 21st, 2024
- Stem cells: Therapy, controversy, and research - Medical News Today - September 4th, 2024
- Stem cell-based therapy for human diseases - PMC - September 4th, 2024
- Bone marrow mesenchymal stem cells in treatment of peripheral nerve ... - September 4th, 2024
- Stem Cell Therapy Mexico: R3 Stem Cell Unveils Innovative and Affordable Non-Invasive Solutions - openPR - September 4th, 2024
- 'Didn't know this would be possible': Autistic teen's mom on stem cell therapy benefits - WZTV - May 5th, 2024
- Putting Stem Cell-Based Therapies in Context | National Institutes of ... - April 8th, 2024
- Eggs from men, sperm from women: Stem cell therapy may just turn reproduction upside down! - The Economic Times - January 17th, 2024
- Stem Cell Therapy: From Idea to Clinical Practice - PMC - December 13th, 2023
- Current state of stem cell-based therapies: an overview - PMC - November 18th, 2023
- Stem Cell Therapy Is It Right for You? Cleveland Clinic - January 31st, 2023
- Stem Cell Therapy | Mellon Center Approach | Cleveland Clinic - January 31st, 2023
- Stem Cell Therapy for Parkinson's: Current Developments - Healthline - December 3rd, 2022
- Canine Stem Cell Therapy Market Size 2022 with a CAGR of % Market Share, prime companies report covers, world business Trends, Statistics, Definition,... - June 16th, 2022
- Global Rheumatoid Arthritis Stem Cell Therapy Market 2022 Swot Analysis by Top Key Vendors, Demand And Forecast Research to 2028 Designer Women -... - June 16th, 2022
- Sutton boy pledges to raise money to help his brother with autism go to America for stem cell therapy - Mansfield and Ashfield Chad - June 16th, 2022
- Japan's five hottest biotech companies in healthcare - Labiotech.eu - June 16th, 2022
- Hemostemix Announces the Incorporation of PreCerv Inc. And a Global Field of Use License to NCP-01 - Yahoo Finance - June 16th, 2022
- Stem cell therapy shows promise in aiding equine wound healing - Horsetalk.co.nz - Horsetalk - April 2nd, 2022
- Rheumatoid Arthritis Stem Cell Therapy Market Assessment, With Major Top Companies Analysis, Geographic Analysis, Growing Opportunities Data By... - April 2nd, 2022
- Jasper Therapeutics to Present Updated Data on JSP191 Conditioning in SCID Patients at the 2022 Clinical Immunology Society Annual Meeting - Yahoo... - April 2nd, 2022
- Talaris therapy ends need for immune drugs in transplant patients - - pharmaphorum - November 7th, 2021
- Safety of Stem Cell Therapy for Chronic Knee Pain Confirmed in New Study - SciTechDaily - August 4th, 2021
- Multiple myeloma stem cell transplant: What happens and more? - Medical News Today - August 4th, 2021
- Animal Stem Cell Therapy Market Research 2021-2027 With Medivet Biologics LLC, VETSTEM BIOPHARMA, J-ARM, US Stem Cell The Manomet Current - The... - August 4th, 2021
- Global Stem Cell Therapy Market to witness exponential proliferation during 2020-2026 The Manomet Current - The Manomet Current - August 4th, 2021
- FDA gives speedy review to Bayer's Parkinson's stem cell therapy - - pharmaphorum - July 21st, 2021
- Stem Cell Therapy Market Analysis of Key Players, End User, Demand and Consumption By 2026 26 Sports - 2x6 Sports - July 21st, 2021
- NanoString Launches nCounter Stem Cell Characterization Panel to Advance the Development of Stem Cell Therapy - Business Wire - June 24th, 2021
- Adipose Tissue Derived Stem Cell Therapy Market New Innovation and Perception 2028 AlloCure, Antria, Celgene, Cellleris SA, Corestem, Intrexon,... - June 24th, 2021
- Jasper Therapeutics and Aruvant Announce Research Collaboration to Study JSP191, an Antibody-Based Conditioning Agent, with ARU-1801, a Novel Gene... - June 24th, 2021
- Global Nerve Repair and Regeneration Devices Market to Reach $11. 8 Billion by 2026 - GlobeNewswire - June 24th, 2021
- Controversial Stem Cell Therapy Has Helped Repair Injured Spinal Cords in 13 Patients - ScienceAlert - March 3rd, 2021
- Cynata tests wound dressing tech for stem cell therapy delivery - The West Australian - March 3rd, 2021
- Stem Cell Injections Could Treat Spinal Cord Injuries | IE - Interesting Engineering - March 3rd, 2021
- NSAIDs to Treat Arthritic Canines Through 2028; Stem Cell Therapies to Invigorate Canine Arthritis T - PharmiWeb.com - March 3rd, 2021
- Overview of stem cells therapy in amyotrophic lateral sclerosis - DocWire News - March 3rd, 2021
- We have a hint it may be possible: Controversial stem cell therapy repaired injured spinal cords in 13 patients - RT - March 3rd, 2021
- Global Stem Cell Therapy Market 2021- Regional Analysis(Consumption, Revenue, Market Share and Growth Rate) and Forecast Till 2027 NeighborWebSJ -... - March 3rd, 2021
- Global Animal Stem Cell Therapy Market 2020 2025 Research Report Segment Outlook, Growth Potentials and Analysis of COVID-19 Worldwide Outbreak KSU... - March 3rd, 2021
- Animal Stem Cell Therapy Market Size 2021 | Global Trends, Business Overview, Challenges, Opportunities and Forecast to 2027 The Bisouv Network - The... - March 3rd, 2021
- Projected Stem Cell Therapy Market Growth After Coronavirus COVID-19 Outbrek Analysis and Forecast (2020-2027) The Bisouv Network - The Bisouv... - March 3rd, 2021
- Stem Cell and PRP Injection for Knee Osteoporosis Pain and Injury Using US Image Guidance - Magazine of Santa Clarita - March 3rd, 2021
- Animal Stem Cell Therapy Market Potential Growth, Share and Demand Analysis of Key Players MediVet Biologic, VETSTEM BIOPHARMA, J-ARM, Celavet NY... - March 3rd, 2021
- Musculoskeletal Disorder Stem Cell Therapy Market Size 2021 | Global Trends, Business Overview, Challenges, Opportunities and Forecast to 2027 The... - March 3rd, 2021
- Exclusive Insights on Stem Cell Therapy for Multiple Sclerosis Market 2021-2026: Latest Trends, Drivers, Strategies and Competitive Landscape The... - March 3rd, 2021
- Stem Cell Therapy Market By Treatment,Application,End Users And Geography Forecast To 2027 The Bisouv Network - The Bisouv Network - March 3rd, 2021
- 10 Best Clinics for Stem Cell Therapy in Thailand [2021 ... - February 14th, 2021
- Therapeutic Solutions International Acquires Stem Cell Therapy That Successfully Completed FDA Double Blind Placebo Controlled Efficacy Study for Lung... - February 14th, 2021
- Outlook on the Cell Therapy Global Market to 2027 - Opportunity Analysis and Industry Forecasts - Yahoo Finance - February 14th, 2021
- Global Stem Cell Therapy Market Set to Reach USD 214.5 Million by 2024 - The Courier - February 14th, 2021
- Magenta Therapeutics to Present Additional Data from Phase 1 MGTA-145 Stem Cell Mobilization Program and Preclinical Updates on Targeting Conditioning... - February 14th, 2021
- Stem Cell Therapy Market Revenue, Key Players, Supply-Demand, Investment Feasibility and Forecast By 2029: Osiris Therapeutics, NuVasive, Chiesi... - February 14th, 2021
- Global Autologous Stem Cell and Non-Stem Cell Based Therapies Market Tendencies, Revenue Forecast and Interesting Opportunities from 2020 to 2025 FLA... - February 14th, 2021
- Dancing on Ice's Colin Jackson to get stem cell op as he's got 'knees of 85-year-old' - Mirror Online - February 1st, 2021
- Stem Cell Therapy Market Size to Reach USD 5,040 Million by 2028 | Rising Public-Private Investments and Developing Regulatory Framework for Stem Cell... - January 31st, 2021
- ProgenCell - Stem Cell Therapies offers an updated Stem Cell Therapy for Anti Aging Protocol - PR Web - January 31st, 2021
- Stem Cell Therapy Market 2021: Global Key Players, Trends, Share, Industry Size, Segmentation, Forecast To 2027 KSU | The Sentinel Newspaper - KSU |... - January 31st, 2021
- ClearPoint Neuro, Inc. Announces Expansion of Pre-Clinical and Translational Development Team to Support Gene and Stem Cell Therapy Partners -... - January 31st, 2021
- Stem Cell Therapy for Diabetes and Related Conditions Market Size |Incredible Possibilities and Growth Analysis and Forecast To 2025 - AlgosOnline - January 31st, 2021
- Stem Cell Therapy Market 2021 Industry Size, Trends, Global Growth, Insights And Forecast Research Report 2026 NeighborWebSJ - NeighborWebSJ - January 31st, 2021
- Animal Stem Cell Therapy Market to witness high growth in near future - Fractovia News - January 31st, 2021
- Regenerative medicine is advancing health care in diverse ways - Hometown Focus - January 23rd, 2021
- Hemostemix Announces the Bread Contract with the Department of Foreign Affairs, Trade & Development Canada - BioSpace - January 23rd, 2021
- Stem Cell Therapy Market Size, Growth Opportunities, Trends, Key Players and Forecast to 2027 - The Courier - January 23rd, 2021
- Animal Stem Cell Therapy Market Size, Business Growth Tactics, Future Strategies, Competitive Outlook and Forecast to 2027 Jumbo News - Jumbo News - January 23rd, 2021
- How Will Global Stem Cell Therapy Market React from 2021 Onwards? - The Courier - January 23rd, 2021
- Impact of COVID-19 on Canine Stem Cell Therapy Market by 2027 |Aratana Therapeutics, Okyanos, Magellan Stem Cells, Stem Cell Vet, VetStem Biopharma -... - January 23rd, 2021
- Impact of COVID-19 on Canine Stem Cell Therapy Market 2021 | Size, Growth, Demand, Opportunities & Forecast To 2027 | VETSTEM BIOPHARMA, Cell... - January 23rd, 2021
- Global Animal Stem Cell Therapy Market Size| Share| Trends and Analysis | Industry Growth Insight By 2025 Globalmarketers.biz Jumbo News - Jumbo... - January 23rd, 2021
- Impacts of COVID 19 on Stem Cell Therapy Market 2021 Size, Demand, Opportunities & Forecast To 2026 - NeighborWebSJ - January 23rd, 2021