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A fluidic device to study directional angiogenesis in complex tissue and organ culture models
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
2009 (Engelska)Ingår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 9, nr 4, s. 529-535Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Many signals that induce angiogenesis have been identified; however, it is still not clear how these signals interact to shape the vascular system. We have developed a fluidic device for generation of molecular gradients in 3-dimensional cultures of complex tissues and organs in order to create an assay for precise induction and guidance of growing blood vessels. The device features a centrally placed culture chamber, flanked by channels attached to a perfusion system used to generate gradients. A separate network of vacuum channels permits reversible attachment of the device to a flat surface. We show that the fluidic device can be used to create growth factor gradients that induce directional angiogenesis in embryonic mouse kidneys and in clusters of differentiating stem cells. These results demonstrate that the device can be used to accurately manipulate complex morphogenetic processes with a high degree of experimental control.

Ort, förlag, år, upplaga, sidor
2009. Vol. 9, nr 4, s. 529-535
Nationell ämneskategori
Medicin och hälsovetenskap Teknik och teknologier
Identifikatorer
URN: urn:nbn:se:uu:diva-89325DOI: 10.1039/b814691hISI: 000263465900005PubMedID: 19190788OAI: oai:DiVA.org:uu-89325DiVA, id: diva2:160096
Tillgänglig från: 2009-02-11 Skapad: 2009-02-11 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
Ingår i avhandling
1. Directing Angiogenesis: Cellular Responses to Gradients in vitro
Öppna denna publikation i ny flik eller fönster >>Directing Angiogenesis: Cellular Responses to Gradients in vitro
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Blood vessels are essential for the delivery of nutrients and oxygen to tissues, as well as for the removal of waste products. Patients with tumors, wounds or diabetes all have active angiogenesis, formation and remodeling of blood vessels, a process that is initiated and manipulated by gradients of secreted signaling proteins.

This thesis describes the development of new microfluidic in vitro assays where directed migration of single endothelial cells and three dimensional vascular structures can be monitored in real time. Combining these assays with live imaging microscopy we have studied the behavior of endothelial cells in gradients of proangiogenic factors as well as directed sprouting in embryonic kidneys and stem cell cultures.

With the 2D assay we have quantified endothelial cell chemotaxis towards FGF2, VEGFA165 and VEGFA121 and we also demonstrate that constant levels of VEGFA165, but not of FGF2, are able to reduce chemokinesis of endothelial cells.

In the 3D migration chamber we have studied directed endothelial cell sprouting in mouse embryonic kidneys and embryoid bodies in response to VEGFA gradients. In both models directed angiogenesis is detected towards increasing levels of growth factor.

Using the microarray technique on differentiating embryonic stem cells we have been able to identify the gene exoc3l2 as potentially involved in angiogenesis and endothelial cell migration and we present evidence that ExoC3l2 is associated with the exocyst complex; an important regulator of cell polarity. We have also shown that siRNA mediated gene silencing of exoc3l2 results in impaired VEGFR2 phosphorylation as well as loss of directionality in response to a VEGFA gradient.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2011. s. 52
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 643
Nyckelord
Angiogenesis, Endothelial cell, Cell migration, Chemotaxis, Gradients, Microfluidics, VEGFA, VEGFR2, Exocyst, Exocytosis
Nationell ämneskategori
Biokemi och molekylärbiologi
Forskningsämne
Medicinsk biokemi
Identifikatorer
urn:nbn:se:uu:diva-145525 (URN)978-91-554-8006-6 (ISBN)
Disputation
2011-04-15, B22, BMC, Husargatan 3, 74123, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Anmärkning
(Faculty of Medicine)Tillgänglig från: 2011-03-08 Skapad: 2011-02-09 Senast uppdaterad: 2011-05-04

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