Traumatic brain injury (TBI) is a form of brain damage caused by an external mechanical force, such as a jolt to the head, leading to impaired brain function. It remains one of the leading causes of disability and mortality worldwide. Each year, it affects an estimated 69 million people and places a substantial burden on healthcare systems. Beyond the initial injury, patients often experience secondary damage, a series of delayed biological responses that include inflammation, reduced blood flow, oxidative stress, and excitotoxicity, which can worsen brain damage and hinder recovery. Despite decades of research, effective treatments that can fully restore brain function remain limited. Most current approaches focus on stabilizing patients or preventing further damage rather than repairing the injured brain.
In a recent review available online on December 22, 2025, and published in Volume 2, Issue 1 of Brain Network Disorders on March 24, 2026, researchers from Zhejiang University, China, present a comprehensive overview of stem cell-based strategies for TBI. The study brings together current advances in stem cell therapy, exosome-based approaches, and tissue engineering, while also outlining key clinical challenges. The study, co-led by Professor Hang Zhou and Professor Gao Chen from the Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, China, emphasizes the growing need for regenerative approaches that go beyond conventional care. “TBI is highly complex, and its pathological heterogeneity continues to limit progress in developing effective therapies,” explains Prof. Zhou. “This highlights the urgent need for treatment strategies that can address multiple aspects of injury and support functional recovery.”
Stem cell therapy has emerged as a promising avenue in regenerative medicine due to its ability to target multiple aspects of injury. Stem cells can self-renew and differentiate into various cell types, including neurons and glial cells. More importantly, they can influence the brain’s microenvironment by releasing signaling molecules that reduce inflammation and support repair. “Neural stem cells can promote brain repair by suppressing neuroinflammation, enhancing angiogenesis, synaptic regeneration, and neural circuit remodeling,” says Prof. Chen. “These combined effects make them a promising approach for restoring damaged brain function.”
In this review, the researchers highlight that the therapeutic effects of stem cells may not rely solely on replacing damaged neurons. Instead, these cells can regulate the injury environment and activate endogenous repair mechanisms. Preclinical studies have shown that different stem cell types, including mesenchymal stem cells and neural stem cells, can improve functional outcomes by enhancing neurogenesis, strengthening synaptic connections, and reducing inflammation.
In addition to cell-based therapies, the researchers discuss the emerging interest in exosomes, small extracellular vesicles released by stem cells. These vesicles carry bioactive molecules such as proteins and microRNAs that influence surrounding cells and promote tissue repair. Because exosomes are cell-free, they may reduce risks such as immune rejection and tumor formation while still delivering therapeutic benefits.
Another promising strategy involves combining stem cells with biomaterial scaffolds. These engineered structures can improve stem cell survival, guide their differentiation, and enhance their retention at the injury site. By mimicking the brain’s natural extracellular environment, scaffolds may further improve the effectiveness of regenerative therapies.
Despite these advances, significant challenges remain. Clinical evidence supporting the effectiveness of stem cell therapies, particularly in severe TBI, is still limited. Questions regarding optimal cell type, dosage, timing, and delivery methods have yet to be fully resolved. Prof. Zhou concludes, “Stem cell-based therapies, along with advances in exosomes and tissue engineering, offer promising directions for brain repair. With further research and well-designed clinical trials, these strategies may move closer to achieving meaningful recovery in patients with traumatic brain injury.”
Overall, the study provides a balanced perspective on the current state of stem cell therapy for TBI. While the field holds considerable promise, further research will be essential to translate these advances into safe, effective, and widely accessible clinical treatments.
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Reference
DOI: 10.1016/j.bnd.2025.09.001
Brain Network Disorders
Literature review
Not applicable
Stem cell therapy for traumatic brain injury: Current advances, clinical challenges, and future directions
24-Mar-2026
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.