Scientists at the University of Rochester<\/b> have developed state-of-the-art microchip systems containing human tissue<\/b>. This technological achievement grants researchers an unprecedented opportunity to study the function of the human brain in detail, both under normal, healthy conditions and during pathological changes such as acute inflammation, infection, or chronic neurodegenerative disorders (e.g., Alzheimer\u2019s disease<\/b>).<\/p>\n
The primary goal of this technology is to replace animal experimentation and ensure maximum accuracy of results for the human body. Led by Professor James McGrath<\/b>, this innovative model, which mimics the interactions between different types of human tissue, is poised to play a crucial role in understanding the function of the Blood-Brain Barrier (BBB)<\/b>\u2014a critical protective boundary for the brain. Since barrier damage is the starting point for many neurological issues, studying it in a controlled and realistic environment is critical for developing new therapeutic approaches.<\/p>\n
Medscriptum conducted an exclusive interview with one of the lead researchers of this scientific achievement, Professor James McGrath<\/b>, who offers an in-depth perspective on the innovation developed by the University of Rochester.<\/p>\n
Professor James McGrath, with extensive experience at MIT<\/b> and Harvard<\/b>, is currently a leading figure on the Biomedical Engineering faculty at the University of Rochester, where he heads the Nanomembrane Research Group (NRG)<\/b>. His team creates microchip systems based on ultrathin silicon nanomembranes that contain human brain tissue.<\/p>\n
Professor McGrath discusses in detail how this technology provides unprecedented accuracy in studying pathologies such as Alzheimer\u2019s or Cytokine Storms<\/b>. Discover how this breakthrough is changing traditional methods and the crucial role assigned to the study of the Blood-Brain Barrier and Pericytes<\/b>.<\/p>\nInterview with Professor James McGrath<\/h3>\n
Your team has created chips containing human tissue that replicate the Blood-Brain Barrier (BBB) model. What prompted this approach, and how does this innovation improve methodology compared to traditional animal models?<\/b><\/p>\n
We have been working on modeling the human Blood-Brain Barrier for a long time. The impetus came from clinicians treating sepsis patients who showed us how devastating this syndrome is\u2014including for those patients who survive but develop persistent cognitive decline<\/b>.<\/p>\n
Despite decades of research on rodents, there are still no approved medications for sepsis<\/b>, primarily because the immune systems of rodents and humans differ so dramatically. Using our tissue chips, which incorporate human cells<\/b>\u2014including immune cells\u2014we can uncover mechanisms of brain injury and barrier dysregulation that are simply inaccessible in animal models. Our approach marries engineering with human immunology to offer a more accurate methodology for studying disease.<\/p>\n
Recent studies have shown how a Cytokine Storm can damage the BBB. Can you describe what happens during these intense immune reactions and how your chips help in identifying the processes that lead to brain damage?<\/b><\/p>\n
During a Cytokine Storm<\/b>, the massive immune signaling originating from the periphery activates the brain’s endothelial cells<\/b>\u2014the cells that form the walls of the blood vessels in the BBB. This hyper-activation makes the barrier permeable and recruits circulating immune cells which enter the brain, escalating inflammation and ultimately leading to neuronal injury<\/b>. Our chip allows us to visually observe and quantitatively measure these processes in real-time<\/b>, revealing the step-by-step transition from systemic inflammation to neurovascular damage\u2014a process that was extremely difficult to analyze in detail using animal models.<\/p>\n
Your research highlights the importance of Pericytes and Microglia in maintaining brain health. How do these cells act to maintain or restore barrier function, and what insights has your innovation provided regarding these interactions?<\/b><\/p>\n
Pericytes<\/b> are increasingly recognized as key stabilizers of the Blood-Brain Barrier, yet their exact contribution has been difficult to pinpoint. They don’t form the barrier themselves, but they provide critical mechanical and biochemical support to the endothelial layer. Using the chips, we deliberately damaged the substrates and showed that: (1) barriers became leaky without pericytes, and (2) pericytes could restore the barrier to a ‘healthy’ level by stiffening these compromised substrates. This gave us the first direct evidence that pericytes exert a physical stabilizing influence<\/b> on the barrier. Simultaneously, we’ve begun to study how Microglia<\/b>\u2014the brain’s resident immune cells\u2014respond to barrier breakdown and regulate repair, noting a coordinated cellular dialogue that protects the neurovascular unit.<\/p>\n
Looking ahead, you aim to use these chips for drug testing and personalized medicine. How will the technology help us assess patient risk before major surgery or chemotherapy and develop ways to mitigate those risks?<\/b><\/p>\n
We are now building isogenic models<\/b> of the BBB and neurovascular unit, where all cell types are derived from a single donor. These genetically matched systems can ultimately model individual responses to events like immunotherapy or major surgeries that carry a risk of brain injury.<\/p>\n
In clinical trials, such chips could be used to balance drug doses, identify high-risk patients, or even exclude those most prone to neurotoxicity<\/b>. We are also testing specific cytokine responses by challenging the chips with blood samples from individuals, creating a fully personalized inflammation-injury model. In combination with multi-donor panels, these chips will be a powerful tool for discovering and optimizing neuroprotective agents<\/b>.<\/p>\n
Finally, what do you believe is the long-term significance of this work? Can chips containing human tissue change the approach to studying and developing therapies for neurodegenerative diseases in ways previously impossible?<\/b><\/p>\n
Neurodegeneration arises from the interaction of genetics, aging, and environmental factors. While these factors determine an individual’s baseline brain health, episodes of systemic inflammation can accelerate decline by triggering BBB breakdown and secondary damage.<\/p>\n
By dissecting the parts of the brain that are resilient<\/b> to inflammatory attacks from those that are vulnerable<\/b>, our work aims to discover effective targets and guide interventions that preserve this resilience. Ultimately, I hope this technology will help more people maintain cognitive health late in life\u2014transforming the way we study, prevent, and treat neurodegenerative diseases.<\/p>\n","protected":false},"excerpt":{"rendered":"
Scientists at the University of Rochester have developed state-of-the-art microchip systems containing human tissue. This technological achievement grants researchers an unprecedented opportunity to study the function of the human brain in detail, both under normal, healthy conditions and during pathological changes such as acute inflammation, infection, or chronic neurodegenerative disorders (e.g., Alzheimer\u2019s disease). The primary […]<\/p>\n","protected":false},"author":2,"featured_media":7794,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1653,1631,1594,1645,1587,1657,1633,1659],"tags":[2340,2341],"class_list":["post-7795","post","type-post","status-publish","format-standard","has-post-thumbnail","category-interview","category-neurology","category-news","category-psychiatry","category-research","category-science","category-surgery","category-technologies","tag-james-mcgrath","tag-microchip-systems"],"acf":[],"_links":{"self":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/7795","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/comments?post=7795"}],"version-history":[{"count":1,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/7795\/revisions"}],"predecessor-version":[{"id":7798,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/posts\/7795\/revisions\/7798"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/media\/7794"}],"wp:attachment":[{"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/media?parent=7795"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/categories?post=7795"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medscriptum.org\/en\/wp-json\/wp\/v2\/tags?post=7795"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}