Publication Date

2016-04-22

Availability

Embargoed

Embargo Period

2018-04-22

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Cancer Biology (Medicine)

Date of Defense

2016-02-23

First Committee Member

Ian K. McNiece

Second Committee Member

Roland Jurecic

Third Committee Member

Keith A. Webster

Fourth Committee Member

Sanjoy Bhattacharya

Fifth Committee Member

Krishna V. Komanduri

Sixth Committee Member

Ralf Landgraf

Abstract

In regenerative medicine, efforts should include utilization of the safest and least invasive methods with the goal of achieving optimal therapeutic outcome. Advancements in stem cell science have triggered the use of cells to cure various disease conditions. However the clinical success of such approaches depends largely on understanding the basic biology of the key players involved- stem cells, stromal cells and their microenvironment. Research shows that stromal cells have key roles in protecting and regulating tissue resident stem cells and maintaining tissue homeostasis. The objective of this dissertation work is to study the role of stromal cells in tissue repair and to find properties of stromal cells relevant for use in regenerative therapy. Many clinical studies have focused on transplantation of isolated and ex vivo expanded stem cells into patients to achieve tissue repair. This study looks at the feasibility of stromal cell mobilization by growth factors and drugs. The effect of mobilized stromal cells was tested in an animal model of liver injury. Further, the properties of stromal cells isolated from different tissue sources were compared. Injections of combinations of granulocyte colony stimulating factor (G-CSF) and AMD3100 (plerixafor) were able to mobilize stromal cells into circulation. This combination also improved survival and tissue function in mice with CCl4 induced liver damage. Stromal cells obtained from different sources were similar in morphology, phenotype and differentiation capacity into MSCs but were functionally different. Heart derived stromal cells and heart stromal cell conditioned media both inhibited proliferation of tumor cells in vitro. These findings present stem cell mobilization as an alternate or adjunct treatment to current regenerative approaches. Unique properties of different stromal cells, like the tumor cell suppression ability of heart stromal cells, will increase our understanding of their biology and enable more educated choices to be made in selection of cell source for regenerative therapies.

Keywords

regenerative medicine; stromal cells; tissue regeneration; G-CSF; AMD3100; miR-206

Available for download on Sunday, April 22, 2018

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