The recruitment mechanisms and beneficial roles of haematopoietic stem cells in murine acute kidney injury

White, Rebecca Lucy (2014). The recruitment mechanisms and beneficial roles of haematopoietic stem cells in murine acute kidney injury. University of Birmingham. Ph.D.

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Abstract

Haematopoietic stem cells (HSCs) can migrate to the injured kidney and aid in tissue repair, however clinical success remains poor and is partially attributed to limited HSC recruitment. This study determined the molecular mechanisms governing HSC recruitment to the ischaemia-reperfusion (IR) injured kidney, whether this recruitment could be enhanced and also any immuno-modulatory effects HSCs may be having on surrounding injured microvasculature. HSC adhesion was significantly enhanced to the IR injured kidney compared to sham; this recruitment was governed by CD49d/VCAM-1 and CD44/HA. KC or SDF-1α pre-treatment enhanced HSC adhesion to the IR kidney. KC and SDF-1α also increased CD44 and CD49d surface clusters on HSCs respectively, and therefore increased HSC adhesion to HA and VCAM-1. Following injection into IR injured mice, HSCs improved blood flow and kidney function in the injured kidney compared to sham. This may be related to inflammatory modulation, as neutrophil recruitment and number of platelet microthrombi were reduced following HSC administration. This is the first study to show that pre-treatment of HSCs increases their recruitment to the site of injury, and that recruitment of HSCs can reduce inflammatory cell infiltration following injury.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):