| Autor: |
Na Geum Lee, Mi-Hee Lim, Jongjin Park, In Cheul Jeung, Byungtae Hwang, Jangwook Lee, Jong-Gil Park, Mi-Young Son, Baek Soo Han, Sung-Jin Yoon, Seon-Jin Lee, Young-Jun Park, Jae Ho Kim, Nam-Kyung Lee, Sang Chul Lee, Jeong-Ki Min |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Bioengineering, Vol 10, Iss 10, p 1132 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2306-5354 |
| DOI: |
10.3390/bioengineering10101132 |
| Popis: |
Blood–brain barrier (BBB) models are important tools for studying CNS drug delivery, brain development, and brain disease. In vitro BBB models have been obtained from animals and immortalized cell lines; however, brain microvascular endothelial cells (BMECs) derived from them have several limitations. Furthermore, obtaining mature brain microvascular endothelial-like cells (BME-like cells) from human pluripotent stem cells (hPSCs) with desirable properties for establishing BBB models has been challenging. Here, we developed an efficient method for differentiating hPSCs into BMECs that are amenable to the development and application of human BBB models. The established conditions provided an environment similar to that occurring during BBB differentiation in the presence of the co-differentiating neural cell population by the modulation of TGF-β and SHH signaling. The developed BME-like cells showed well-organized tight junctions, appropriate expression of nutrient transporters, and polarized efflux transporter activity. In addition, BME-like cells responded to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance. Moreover, the BME-like cells exhibited an immune quiescent property of BBB endothelial cells by decreasing the expression of adhesion molecules. Therefore, our novel cellular platform could be useful for drug screening and the development of brain-permeable pharmaceuticals. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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