期刊
JOURNAL OF PERSONALIZED MEDICINE
卷 12, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/jpm12020148
关键词
microphysiological systems; blood-neural barriers; neurovascular unit; disease modeling; 3D models; organ-on-a-chip; inner blood-retinal barrier
Blood-neural barriers are crucial in regulating nutrient supply and preventing neurotoxicity. Human in vitro models, such as microphysiological systems (MPS), are being developed to better understand neurodegenerative diseases. Recent advances in neurovascular barrier modeling using human cells have shown potential for modeling the inner blood-retinal barrier (iBRB) and can be leveraged in developing new iBRB models. Personalized cellular inputs and improved pre-clinical testing can be achieved through MPS-based strategies.
Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood-brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules can be accompanied by neurodegeneration. Therefore, pre-clinical research requires human in vitro models that elucidate pathophysiological mechanisms and support drug discovery, to add to animal in vivo modeling that poorly predict patient responses. Advanced cellular models such as microphysiological systems (MPS) recapitulate tissue organization and function in many organ-specific contexts, providing physiological relevance, potential for customization to different population groups, and scalability for drug screening purposes. While human-based MPS have been developed for tissues such as lung, gut, brain and tumors, few comprehensive models exist for ocular tissues and iBRB modeling. Recent BBB in vitro models using human cells of the neurovascular unit (NVU) showed physiological morphology and permeability values, and reproduced brain neurological disorder phenotypes that could be applicable to modeling the iBRB. Here, we describe similarities between iBRB and BBB properties, compare existing neurovascular barrier models, propose leverage of MPS-based strategies to develop new iBRB models, and explore potentials to personalize cellular inputs and improve pre-clinical testing.
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