In vitro processing of human bone marrow derived mesenchymal stem cells to enhance delivery in liver disease

Garg, Abhilok (2013). In vitro processing of human bone marrow derived mesenchymal stem cells to enhance delivery in liver disease. University of Birmingham. Ph.D.

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Abstract

Currently the only effective treatment for end stage liver disease is transplantation together with immune-modulating drugs. Human bone marrow derived mesenchymal stem cells (MSC) have been shown to suppress inflammation, potentiate regeneration and act as vectors for gene therapy. Thus, MSC infusions offer an attractive potential therapy for treating liver disease. However a number of obstacles exist in MSC delivery before they can be used therapeutically. Although MSC can migrate to sites of injury after in vivo administration, their engraftment within the liver is often poor, potentially limiting their therapeutic action. I have shown that detaching MSC from culture using non-enzymatic methods is superior in retaining surface chemokine receptor expression. Furthermore, I have shown that these receptors are functional in migration and attachment assays both in vitro and in vivo in carbon-tetrachloride induced liver injury. TGFβ1 stimulated MSC were able to further enhance engraftment via up-regulation of surface CXCR3. Additionally the potent immunosuppressive properties of MSC, mediated via Prostaglandin E2, were enhanced after TGFβ1 stimulation. Thus my studies demonstrate that manipulation of MSC through careful choice of detachment methods and exogenous cytokine stimulation can improve their engraftment in injured liver and their immunosuppressive properties with implications for improving the efficacy of MSC therapy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):