USP CAR-T Therapy Breakthrough: Reduces Liver Fibrosis in Mice

Revolutionary USP Study Showcases In Vivo CAR-T Therapy Reducing Liver Fibrosis in Mice

In a landmark achievement for biomedical research, scientists from the University of São Paulo (USP) have demonstrated that chimeric antigen receptor T-cell (CAR-T) therapy, generated directly within the body, can significantly reduce hepatic fibrosis in a mouse model of metabolic dysfunction-associated steatohepatitis (MASH). Published in Science Translational Medicine on January 21, 2026, the study titled "Anti-FAP CAR T cells produced in vivo reduce fibrosis and restore liver homeostasis in metabolic dysfunction–associated steatohepatitis" highlights an innovative approach using lipid nanoparticles to deliver CAR messenger RNA (mRNA), bypassing traditional ex vivo cell manufacturing. This collaboration between USP's Faculty of Veterinary Medicine and Animal Science (FMVZ) and international partners like the University of Pennsylvania marks a potential paradigm shift in treating chronic liver conditions.

The research addresses a critical gap: MASH, previously known as non-alcoholic steatohepatitis (NASH), affects over 350 million people globally and is projected to rise in prevalence in Brazil from 7.19% to 7.52% among adults by 2040. In Brazil, liver diseases claim around 40,000 lives annually, underscoring the urgency for new therapies. Led by Bruno Cogliati, PhD from USP, the team targeted fibroblast activation protein (FAP) on activated hepatic stellate cells (HSCs), the primary drivers of fibrosis.

Understanding Hepatic Fibrosis and the MASH Crisis

Hepatic fibrosis occurs when excessive scar tissue, primarily collagen, accumulates in the liver, impairing its function. It is a common endpoint of chronic liver injuries from alcohol abuse, viral hepatitis (B and C), or metabolic factors like obesity and type 2 diabetes. In MASH, fat buildup triggers inflammation and HSC activation, leading to fibrosis that can progress to cirrhosis or hepatocellular carcinoma if unchecked.

Globally, MASH represents a ticking time bomb, with no approved antifibrotic drugs. In Brazil, rising obesity rates exacerbate the issue, mirroring global trends where advanced fibrosis prevalence in type 2 diabetes patients varies widely but remains alarmingly high. Traditional treatments focus on lifestyle changes or symptom management, but they fail to reverse scarring. This USP-led innovation offers hope by precisely eliminating fibrogenic cells.

What Are CAR-T Cells? From Cancer to Fibrosis

CAR-T therapy involves engineering a patient's T cells (a type of immune cell) to express chimeric antigen receptors (CARs) that recognize specific proteins on diseased cells. Originally approved for blood cancers like leukemia, where ex vivo-modified CAR-T cells are reinfused after chemotherapy, the approach has limitations: high costs (hundreds of thousands per treatment), manufacturing complexity, and risks like cytokine release syndrome (CRS).

• Ex vivo process: Extract T cells, genetically modify, expand in lab, reinfuse.
• In vivo advantage: Direct delivery via nanoparticles, transient expression, lower toxicity.

USP researchers adapted this for fibrosis, building on prior cardiac fibrosis work, targeting FAP—a protein upregulated on activated fibroblasts but absent in healthy tissue.

The Groundbreaking In Vivo Delivery Method

The study's novelty lies in using anti-CD5-targeted lipid nanoparticles (t-LNPs) loaded with anti-FAP CAR mRNA. These nanoparticles home to T cells in vivo, instructing them to produce CARs transiently. Unlike viral vectors, mRNA degrades naturally, ensuring short-term action—ideal for fibrosis reversal without permanent immune alterations.

This builds on lipid nanoparticle success in COVID-19 vaccines, now repurposed for precision immunotherapy. Prior developments include cardiac fibrosis reduction in mice, but liver application is unprecedented.

Detailed Methodology: Mouse Model and Experiments

Mice were induced into MASH via a six-week Western diet (high fat, carbs, sugars) plus hepatotoxin and sugar water, mimicking human metabolic disease. A single tail-vein injection of t-LNPs followed.

• 18 hours post-injection: CAR-T cells detected via flow cytometry.
• 30 days: Fibrosis assessed by Sirius Red staining, digital pathology, single-nucleus RNA-seq.
• Controls: Untreated MASH mice showed progression; therapy group exhibited HSC depletion, reduced collagen.

FAP specificity confirmed in human and mouse MASH livers, sparing healthy HSCs essential for regeneration.

Impressive Results: Fibrosis Reduction and Liver Restoration

The therapy depleted profibrogenic HSCs, slashing fibrosis scores. Beyond direct effects, non-cell-autonomous modulation improved immune infiltration, endothelial function, and hepatocyte health, curbing inflammation. By day 30, CAR-T cells cleared naturally, minimizing risks. No adverse events noted, unlike ex vivo CAR-T.

"Once fibrosis is reduced, no more activated fibroblasts remain, but the body retains capacity for healing elsewhere," notes Cogliati.

Spotlight on Bruno Cogliati and USP's Research Excellence

Bruno Cogliati, professor at USP's FMVZ Department of Pathology, led the Brazilian contingent in this international effort. His expertise in liver pathology bridges veterinary and human medicine, fostering translational research. USP's Ribeirão Preto campus, home to advanced centers like Hemocentro, excels in cell therapy, producing CAR-T for cancers locally.Rate professors like Cogliati and explore opportunities at Brazil's top institutions via AcademicJobs Brazil listings.

This publication underscores USP's global standing, with FMVZ contributing to high-impact journals amid Brazil's growing biotech scene.

Therapeutic Implications and Path to Clinics

For MASH patients, this offers a one-dose potential cure, avoiding transplants. Transient nature suits chronic fibrosis without lifelong immunosuppression. Challenges: Scaling human trials, optimizing dosing, monitoring off-target effects.Read the full study. Similar in vivo CAR-T advances target IPF and cardiac fibrosis.

In Brazil, where liver disease burdens SUS, local production could democratize access, echoing Hemocentro's cancer CAR-T trials.

Brazil's Liver Disease Burden and Research Momentum

Brazil faces escalating liver woes: 40,716 deaths in 2020 alone, with NAFLD/MASH rising amid obesity epidemic. USP's work positions Brazil as a fibrosis therapy leader. For aspiring researchers, higher ed research jobs in immunology and nanomedicine abound.

Future Outlook: Human Trials and Beyond

Preclinical success paves for IND filings. Broader applications: Kidney, lung fibrosis. In vivo CAR-T via LNPs revolutionizes gene therapy, cheaper and faster than viral methods. USP collaborations signal Brazil's biotech rise.

Photo by Devi Puspita Amartha Yahya on Unsplash

Career Opportunities in CAR-T and Liver Research

This study spotlights demand for experts in cell/gene therapy. Brazil's universities seek postdocs, faculty in biotech. Check postdoc positions, research assistants. Craft your academic CV for success. Engage via Rate My Professor.

Explore university jobs and higher ed careers to join innovations like this.