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Continuous Monitori...
Continuous Monitoring Reveals Protective Effects of N‐Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit
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- Matthiesen, Isabelle (author)
- KTH,Mikro- och nanosystemteknik
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- Voulgaris, Dimitrios, 1990- (author)
- KTH,Mikro- och nanosystemteknik
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- Nikolakopoulou, Polyxeni (author)
- AIMES, Center for Integrated Medical and Engineering Sciences Department of Neuroscience Karolinska Institute Solnavägen 9/B8 Solna 171 65 Sweden
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- Winkler, Thomas, Ph.D. (author)
- KTH,Mikro- och nanosystemteknik
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- Herland, Anna (author)
- Karolinska Institutet,KTH,Mikro- och nanosystemteknik
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(creator_code:org_t)
- 2021-06-26
- 2021
- English.
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In: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 17:32, s. 2101785-
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Abstract
Subject headings
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- Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human-like models for biopharmaceutical research. In this study, the first such model of the blood-brain barrier (BBB-on-chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)-derived cells and continuous barrier integrity monitoring with <2 min temporal resolution is reported. Its capabilities are showcased in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off-stoichiometry thiol–ene–epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell–substrate endothelial resistance monitoring allows for capturing the formation and breakdown of the BBB model, which consists of cocultured hiPSC-derived endothelial-like and astrocyte-like cells. Clear cellular disruption is observed when exposing the BBB-on-chip to the nitrosative stressor linsidomine, and the barrier permeability and barrier-protective effects of the antioxidant N-acetylcysteine amide are reported. Using metabolomic network analysis reveals further drug-induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like this opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human-derived cells and providing high-resolution temporal readouts that can help in pharmacodynamic studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Elektroteknik och elektronik -- Annan elektroteknik och elektronik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Electrical Engineering, Electronic Engineering, Information Engineering -- Other Electrical Engineering, Electronic Engineering, Information Engineering (hsv//eng)
Keyword
- Biomaterials
- Biotechnology
- General Materials Science
- General Chemistry
- Electrical Engineering
- Elektro- och systemteknik
- Bioteknologi
- Biotechnology
Publication and Content Type
- ref (subject category)
- art (subject category)
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