Studies of recruitment and migration of mesenchymal stem cells

Alanazi, Asma (2016). Studies of recruitment and migration of mesenchymal stem cells. University of Birmingham. Ph.D.

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Abstract

Mesenchymal stem cells (MSC) are used in therapy by injection into the blood. Adhesion and migration from flowing blood may be critical steps for their recruitment in the microvasculature. We aimed to understand how MSC from different sources might 'home' to injured tissue. MSC from Wharton’s jelly(WJMSC), bone marrow(BMMSC) or trabecular bone(TBMSC) were suspended in culture medium or added to whole blood, and perfused through capillaries coated with matrix proteins (collagen or fibronectin)or P- or E-selectin. Initial comparisons showed that none of the isolated MSC adhered to selectins even at low shear rate. All of the different cells were able to adhere to collagen or fibronectin at wall shear rates up to about 70s-1, with adhesion in the order WJMSC>BMMSC>TBMSC. Although BMMSC spread more efficiently than WJMSC, the WJMSC migrated faster through 8μm pore filters. In whole blood, MSC failed to bind to fibronectin, while the fibronectin itself became covered in a single layer of spread platelets. When perfused over collagen, only WJMSC were found to attach, forming aggregates with platelets on the surface. Adhesion of MSC to matrix proteins and to platelets involved both β1- and β3-integrins. Platelets used glycoproteins GpIb and GpIIbIIIa to adhere and aggregate on collagen, and GpIIbIIIa to adhere and spread on fibronectin, but these receptors did not support the interaction between MSC and platelets. These results show intrinsic differences in adhesion and migration of different MSC, including interaction with platelets that are predicted to influence their behavior in vivo and therapeutic effectiveness.

Type of Work:	Thesis (Doctorates > Ph.D.)
Award Type:	Doctorates > Ph.D.
Supervisor(s):	Supervisor(s) Email ORCID Nash, G. B. (Gerard B.) UNSPECIFIED UNSPECIFIED
Licence:
College/Faculty:	Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department:	Institute of Cardiovascular Sciences
Funders:	None/not applicable
Subjects:	R Medicine > RC Internal medicine
URI:	http://etheses.bham.ac.uk/id/eprint/7112

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