X-TEL utilizes an engineered Neurovascular Unit model (NVU chip) as an efficient experimental platform to address challenging questions in the field of Neuroscience.
(i) NVU chip design. (ii) 8 chips on a 75×25 mm glass slide. (iii) A cross-sectional view with cell distribution. (iv-v) Immunofluorescence (IF) images showing top (iv) and perspective (v) views. GFAP: astrocyte marker. CD31: endothelial cell marker. Scale bars: 100 µm.
Cancer angiogenesis in the NVU chip. Red: Endothelial cells. Magenta: Cancer cells.
Brain Tumor Models for Advancing Immunotherapy
Brain tumors are uniquely challenging due to the difficulty of removing cancer-infiltrated tissues without compromising brain function. Immunotherapy offers a promising solution, targeting cancer cells while preserving healthy tissue. However, the blood-brain barrier (BBB) plays a critical role in shaping the brain’s immune environment, limiting immune cell access and contributing to an immunosuppressive tumor microenvironment that enables immune evasion. Our lab develops advanced human cell-based brain tumor models to study the interaction between the BBB and immune responses. By identifying biomarkers of immune suppression and designing biomarker-specific immunotherapies, we aim to advance personalized treatments for brain tumor patients.
Brain cancer cells (red) migrate though an engineered vasculature.
Deciphering Organ Specificity in Cancer Metastasis
Different types of cancer cells exhibit distinct preferences for metastasizing to specific organs. The vasculature plays a critical role in enabling cancer cells to detach from the primary tumor, travel through the circulatory system, and establish secondary tumors in target organs. Our lab is developing cutting-edge microfluidic models that replicate the organ-specific nature of cancer metastasis. These models allow us to investigate how the vasculature facilitates cross-communication between cancer cells and the microenvironments of specific organs. By identifying tissue-specific signals that drive metastatic progression, our research aims to uncover novel therapeutic targets and strategies to combat organ-specific cancer metastasis.
Amyloid deposition (green) in the NVU chip. Red: Endothelial cells. Magenta: Microglia
Role of blood-brain barrier (BBB) in Alzheimer’s Disease (AD)
The BBB is vital for maintaining cognitive function by regulating the exchange of nutrients, waste, and immune cells between the bloodstream and the brain. Its dysfunction is an early hallmark of AD, characterized by reduced cerebral blood flow and amyloid plaque accumulation in both brain tissue and the walls of cerebral blood vessels. These changes compromise the BBB’s integrity, exacerbating neurodegeneration and cognitive decline. Our lab develops advanced microfluidic models to replicate the BBB and its interactions with brain tissue under disease-like conditions. We focus on understanding how blood flow dynamics, amyloid plaque formation, and vascular abnormalities contribute to BBB dysfunction and drive AD progression. By uncovering the mechanisms behind BBB dysfunction, we aim to identify therapeutic strategies to restore its integrity, reduce amyloid plaque deposition, and mitigate disease progression.
Neurogenesis induced by drug-releasing microparticles.
Engineered Ischemic Stroke Model for Advancing Stem Cell Therapy
Stem cell therapy is emerging as a promising treatment for stroke patients, yet the mechanisms and key factors underlying its clinical efficacy remain poorly understood, posing challenges for optimizing therapeutic administration. In most clinical trials, stem or progenitor cells are delivered through intravascular routes, making their efficacy critically dependent on how the neurovascular unit (NVU) responds to these cells. Our lab is developing an engineered brain model that replicates the ischemic stroke microenvironment to study the natural interactions between stem/progenitor cells and the host cells of the NVU during post-stroke neuroregeneration. This model provides a time- and cost-efficient platform to identify and test critical factors influencing the success of stem cell therapies, with the ultimate goal of improving their clinical outcomes for stroke patients.
