Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature.
Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature.
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DOI：
10.3390/jpm12020148
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发表时间：
2022-01-24
影响因子：
--
通讯作者：
Ragelle H
中科院分区：
文献类型：
--
作者：
Maurissen TL;Pavlou G;Bichsel C;Villaseñor R;Kamm RD;Ragelle H
血神经屏障调节神经组织的营养供应，防止神经毒性。特别是，内血视网膜屏障（iBRB）和血脑屏障（BBB）在发育中有共同的起源，在成人组织中有相似的形态和功能，而屏障破坏和神经毒性分子的泄漏可伴随着神经变性。因此，临床前研究需要阐明病理生理学机制和支持药物发现的人类体外模型，以补充预测患者反应较差的动物体内模型。先进的细胞模型，如微生理系统（MPS）概括了组织的组织和功能，在许多器官特异性的情况下，提供生理相关性，定制不同人群的潜力，和药物筛选目的的可扩展性。虽然已经为肺、肠、脑和肿瘤等组织开发了基于人类的MPS，但很少有用于眼组织和iBRB建模的综合模型。最近的BBB体外模型，使用人类细胞的神经血管单位（NVU）显示生理形态和渗透性值，并再现脑神经系统疾病的表型，可适用于建模的iBRB。在这里，我们描述了iBRB和BBB属性之间的相似性，比较现有的神经血管屏障模型，提出利用基于MPS的策略来开发新的iBRB模型，并探索个性化细胞输入和改善临床前测试的潜力。
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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影响因子：
64.5
作者：
Cowan CS;Renner M;De Gennaro M;Gross-Scherf B;Goldblum D;Hou Y;Munz M;Rodrigues TM;Krol J;Szikra T;Cuttat R;Waldt A;Papasaikas P;Diggelmann R;Patino-Alvarez CP;Galliker P;Spirig SE;Pavlinic D;Gerber-Hollbach N;Schuierer S;Srdanovic A;Balogh M;Panero R;Kusnyerik A;Szabo A;Stadler MB;Orgül S;Picelli S;Hasler PW;Hierlemann A;Scholl HPN;Roma G;Nigsch F;Roska B
通讯作者：
Roska B
影响因子：
4.6
作者：
Bang S;Lee SR;Ko J;Son K;Tahk D;Ahn J;Im C;Jeon NL
通讯作者：
Jeon NL
影响因子：
82.9
作者：
Blanchard JW;Bula M;Davila-Velderrain J;Akay LA;Zhu L;Frank A;Victor MB;Bonner JM;Mathys H;Lin YT;Ko T;Bennett DA;Cam HP;Kellis M;Tsai LH
通讯作者：
Tsai LH
影响因子：
16.2
作者：
Andreone BJ;Chow BW;Tata A;Lacoste B;Ben-Zvi A;Bullock K;Deik AA;Ginty DD;Clish CB;Gu C
通讯作者：
Gu C
影响因子：
3.2
作者：
Brown, Jacquelyn A.;Pensabene, Virginia;Wikswo, John P.
通讯作者：
Wikswo, John P.