Investigating Blood-brain Barrier (BBB) Signaling Cues through a Human Pluripotent Stem Cell (HPSC)-derived Tissue Model of the BBB
Başlık:
Investigating Blood-brain Barrier (BBB) Signaling Cues through a Human Pluripotent Stem Cell (HPSC)-derived Tissue Model of the BBB
Yazar:
Stebbins, Matthew James, author.
ISBN:
9780438159631
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (167 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Sean P. Palecek; Eric V. Shusta Committee members: Randolph S. Ashton; Brian F. Pfleger; John Yin.
Özet:
The blood brain barrier (BBB) is critical to central nervous system (CNS) health by maintaining brain homeostasis. On the macroscopic level, it is comprised of blood vessels that vascularize the CNS, but at the macroscopic level, is comprised of brain microvascular endothelial cells (BMECs), which line CNS capillaries and provide the physical barrier of the BBB. Peripheral cell types of the neurovascular unit, including pericytes, astrocytes, and neurons, provide signaling cues to induce and maintain BMEC barrier properties. CNS capillaries provide an immense surface area and proximity to CNS neurons, making them an ideal target of CNS drug delivery. However, the BBB restricts material transport across the BBB and creates a bottleneck for CNS drug development. In addition, BBB dysfunction is noted in several CNS diseases, including stroke, multiple sclerosis, and Alzheimer's disease.
Human pluripotent stem cell (hPSC)-derived BBB models offer a scalable and renewable source of BMEC-like cells for investigating mechanisms implicated in BBB health and disease, while also offering the potential to high throughput screen BBB therapeutics for CNS entry. This body of work investigates signaling pathways implicated in BBB development and maintenance to improve model characteristics for drug screening studies and identify potential signaling targets to restore BBB function in disease. Through this work, we identified components of retinoic acid and BMP signaling that can improve hPSC-derived BMEC fidelity. In addition, we developed a method to create hPSC-derived pericyte-like cells of the neurovascular unit and incorporate these cells into a previously established iPSC-BMEC/astrocyte/neuron model of the neurovascular unit. This body of work has identified novel signaling mechanisms for future translational studies and created an iPSC-pericyte/BMEC model for future patient-specific CNS disease studies.
Notlar:
School code: 0262
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(687927.1) | 687927-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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