Evaluation of Cell‐Penetrating Peptides Using Microfluidic In Vitro 3D Brain Endothelial Barrier

Chung, Bohye; Kim, Jae-Hoon; Nam, Jong Hee; Kim, Hyunho; Jeong, Yeju; Liu, Hui Wen; Cho, Youngkyu; Kim, Yong Ho; Oh, Hyun Joo; Chung, Seok

doi:10.1002/mabi.201900425

Cited by 7 publications

(12 citation statements)

References 57 publications

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“…3-D microfluidics based BBB models have been reported in a few studies (Supplementary Figures S3-S5) (Linville et al, 2019;Vatine et al, 2019;Ahn et al, 2020;Chung et al, 2020;Chen X et al, 2021). These models can create a 3D tubular geometry (e.g., using collagen hydrogel) and introduce fluid flow in the tubular structure (e.g., using microfluidics), better mimicking the brain microvasculature.…”

Section: Discussionmentioning

confidence: 99%

Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-Culture From Human Stem Cells

et al. 2022

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Background: Recently, the in vitro blood–brain barrier (BBB) models derived from human pluripotent stem cells have been given extensive attention in therapeutics due to the implications they have with the health of the central nervous system. It is essential to create an accurate BBB model in vitro in order to better understand the properties of the BBB, and how it can respond to inflammatory stimulation and be passed by targeted or non-targeted cell therapeutics, more specifically extracellular vesicles.Methods: Brain-specific pericytes (iPCs) were differentiated from iPSK3 cells using dual SMAD signaling inhibitors and Wnt activation plus fibroblast growth factor 2 (FGF-2). The derived cells were characterized by immunostaining, flow cytometry, and RT-PCR. In parallel, blood vessels organoids were derived using Wnt activation, BMP4, FGF2, VEGF, and SB431542. The organoids were replated and treated with retinoic acid to enhance the blood–brain barrier (BBB) features in the differentiated brain endothelial cells (iECs). Co-culture was performed for iPCs and iECs in the transwell system and 3D microfluidics channels.Results: The derived iPCs expressed common markers PDGFRb and NG2, and brain-specific genes FOXF2, ABCC9, KCNJ8, and ZIC1. The derived iECs expressed common endothelial cell markers CD31, VE-cadherin, and BBB-associated genes BRCP, GLUT-1, PGP, ABCC1, OCLN, and SLC2A1. The co-culture of the two cell types responded to the stimulation of amyloid β42 oligomers by the upregulation of the expression of TNFa, IL6, NFKB, Casp3, SOD2, and TP53. The co-culture also showed the property of trans-endothelial electrical resistance. The proof of concept vascularization strategy was demonstrated in a 3D microfluidics-based device.Conclusion: The derived iPCs and iECs have brain-specific properties, and the co-culture of iPCs and iECs provides an in vitro BBB model that show inflammatory response. This study has significance in establishing micro-physiological systems for neurological disease modeling and drug screening.

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Section: Discussionmentioning

confidence: 99%

Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-Culture From Human Stem Cells

et al. 2022

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“…In recent years, there has been a proliferation of novel therapeutic approaches, such as gene therapy, protein therapy, nanomaterial therapy, that have been proposed and explored to address these challenges. 54,55 These therapeutic approaches aim to prevent and treat CNS disorders by modifying or repairing abnormal genes or proteins, as well as utilizing nanomaterials with specific properties and functions. The development of drug carriers capable of penetrating the CNS and exerting therapeutic effects is of utmost importance, given the intricate nature of the CNS barrier.…”

Section: ■ Cpps For Cns Diseases Treatmentmentioning

confidence: 99%

Cell-Penetrating Peptides-Mediated Therapeutic Agents Delivery into the Central Nervous System

Wei,

Bao,

Wang

et al. 2024

ACS Materials Lett.

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There has been a significant increase in the prevalence of central nervous system (CNS) disorders, resulting in a considerable decrease in the overall well-being for affected individuals. Moreover, the therapeutic effectiveness of CNS diseases is greatly impeded by the inability of the majority of small molecule drugs and almost all large molecule drugs to penetrate the brain barrier. Therefore, it is crucial to develop an efficient drug delivery system to effectively treat CNS disorders by transporting therapeutic agents to the CNS. Cell-penetrating peptides (CPPs), which are well-known for their efficient membrane penetration capabilities and their ability to facilitate the rapid passage of therapeutic drugs across the brain barrier, offer a potential strategy for the transportation of macromolecules across the brain barrier. This study has provided a comprehensive overview of the utilization of CPP-mediated therapeutic agents in the management of CNS diseases and summarized the recent advancements in clinic, aiming to establish a scientific foundation for the application of CPPs in the treatment of CNS diseases.

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“…The gBM on COL1 allowed the formation of a stable gEC monolayer, preventing gECs from sprouting and invading the COL1 hydrogel. The gECs cultured in the channel under conventional EC monolayer formation protocols [18][19][20] did not form a stable barrier structure, showing detachment from COL1 and sprouting (Fig. S3 †).…”

Section: D Glomerular Endothelial Monolayer Construction By Tunable G...mentioning

confidence: 99%

“…The GFB model was developed from the protocols of hydrogel compartmentalization in microfluidic channels 16 and 3D confluent monolayer formation on the BM-deposited hydrogel. [17][18][19] Our GFB model has two features distinct from the previous microfluidic GFB model: the tunable gBM deposition and the 3D cultured podocytes. The thickness of the gBM can be precisely tuned by adjusting the deposition time and sensitively regulated the gECs function similar to the in vivo situation.…”

Section: Introductionmentioning

confidence: 99%

Glomerular filtration barrier modeling on a chip with tunable basement membrane deposition and 3D cultured podocytes

Kim¹,

Kim²,

Kang³

et al. 2023

Lab Chip

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Evaluation of Cell‐Penetrating Peptides Using Microfluidic In Vitro 3D Brain Endothelial Barrier

Cited by 7 publications

References 57 publications

Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-Culture From Human Stem Cells

Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-Culture From Human Stem Cells

Cell-Penetrating Peptides-Mediated Therapeutic Agents Delivery into the Central Nervous System

Glomerular filtration barrier modeling on a chip with tunable basement membrane deposition and 3D cultured podocytes

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