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Characterizing Hypoxia And Its Behavioral Effects In 3-Dimensional Cell Aggregates, Matthew Lorincz Skiles
Characterizing Hypoxia And Its Behavioral Effects In 3-Dimensional Cell Aggregates, Matthew Lorincz Skiles
Theses and Dissertations
Cell transplantation can be considered a regenerative therapy, an intervention which attempts to replace or restore the function of compromised tissue by harnessing innate properties of cells that cannot be replicated artificially. For such therapies to succeed, it will be necessary to understand and closely match the physiological conditions that govern cell behaviors in vivo. One important factor is low oxygen tension, termed hypoxia, which is often overlooked in vitro. Because oxygen insufficiency can lead to cell death, hypoxia has traditionally been viewed as a negative condition. However, hypoxia can also serve as a potent regulator of crucial cell behaviors …
Effect Of Physiological Oxygen Levels On Osteogenic Differentiation Of Adipose-Derived Stem Cells, Suchit Sahai
Effect Of Physiological Oxygen Levels On Osteogenic Differentiation Of Adipose-Derived Stem Cells, Suchit Sahai
Theses and Dissertations
Regenerative medicine presents exciting strategies for healing critical-size bone defects through the implantation of cells and biocompatible scaffolds. Most in vitro studies are performed in atmospheric oxygen conditions (~20%), which do not accurately mimic the CSD microenvironment. Due to damage to the vasculature at CSDs, oxygen levels fall into the hypoxic range (<5%), which can impact viability, proliferation and differentiation of the cells employed for bone regeneration. Understanding the cellular responses to hypoxia has grown primarily from study of individual molecular factors. The master regulator of adaptive responses to low oxygen availability is the nuclear factor, hypoxia-inducible factor-1. HIF-1 is a heterodimeric protein, stable below 6% O2 condition in the nucleus and has been shown to play a role in angiogenic-osteogenic coupling. We have developed a responsive, fluorescent, hypoxia detection system and determined whether HIF activity can be tracked in both 2-D and 3-D cultures. Adipose-derived stem cells (ASCs) were selected due to their broad utilization in tissue engineering strategies and characterized the influence of HIF signaling on its phenotype. The work done identified that of hypoxia impaired osteogenic differentiation of ASCs in both 2-D and 3-D cultures and HIF-1 did not mediate this effect. Ischemic preconditioning (IPC) strategy and varied protocols used represents a clinically feasible manipulation of cell preparation to help the survival of implanted ASCs and accelerate osteogenic differentiation at physiological oxygen levels.