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The cancer stem cell hypothesis has been used to explain many cancer complications resulting in poor patient outcomes including induced drug resistance, metastases to distant organs, and tumor recurrence. While the validity of the cancer stem cell model continues to be the cause of much scientific debate, a number of putative cancer stem cell markers have been identified making studies concerning the targeting of cancer stem cells possible. In this review, a number of identifying properties of cancer stem cells have been outlined including properties contributing to the drug resistance and metastatic potential commonly observed in supposed cancer stem cells. Due to cancer stem cells' numerous survival mechanisms, the diversity of cancer stem cell markers between cancer types and tissues, and the prevalence of cancer stem cell markers among healthy stem and somatic cells, it is likely that currently utilized treatments will continue to fail to eradicate cancer stem cells. The successful treatment of cancer stem cells will rely upon the development of anti-neoplastic drugs capable of influencing many cellular mechanisms simultaneously in order to prevent the survival of this evasive subpopulation. Natural compounds represent a historically rich source of novel, biologically active compounds which are able to interact with a large number of cellular targets while limiting the painful side-effects commonly associated with cancer treatment. A brief review of select natural products that have been demonstrated to diminish the clinically devastating properties of cancer stem cells or to induce cancer stem cell death is also presented.

Tissue engineering uses various approaches to restore bone loss and heal critical-size defects resulting from trauma, infection, tumor resection or other musculoskeletal diseases. The success of bone tissue engineering strategies critically depends on the extent of blood vessel infiltration into the scaffolds. It has been demonstrated that blood vessel invasion from the host tissue into scaffolds is limited to a depth of several hundred micrometers. Limited vessel perfusion restricts the formation of bone in central regions of the scaffold, leads to loss of cell viability in this region and ultimately does not support healing of the defect. This review addresses the importance of vascularization in bone tissue engineering, discusses the key factors regulating the process of angiogenesis, and provides an overview of current approaches to direct blood vessel formation in biomaterials.

The field of tissue engineering s to regenerate natural tissues and create new tissues using combinations of living cells, biomaterials and signaling molecules. One of the important requirements for biomaterials is that they allow for development of healthy, internal capillary networks. The objective of this project was to explore the underlying mechanisms that control vascular growth into porous biomaterials through a co-operation between experimentation and mathematical modeling.We developed a a discrete probabilistic mathematical model of cell migration and vascular growth into porous biomaterials. Some of the highlight results of this study included the following: (i) transience in chemoattractant secretion profiles determined the effectiveness of cell motility and cell-to-cell signaling, (ii) tuning the pore surface reactivity to angiogenic factors offered a possible mechanism to hasten the speed of cell migration and tissue ingrowth, and (iii) optimal release durations of an angiogenic growth factor induced deeper vascular growth into the scaffold.The experimental part of this project aimed at exploring the variables that influence the extent of vascular growth in 3D porous poly(1actide-co-glycolide) (PLAGA) sintered microsphere scaffolds. In addition, we designed a combined gene-therapy/cell- transplantation strategy to induce vascular ingrowth. Some of the highlight results of this work were: (i) PLAGA scaffolds supported the growth and biological functions of endothelial cells and adipose derived stromal cells (ADSCs), (ii) vascular endothelial growth factor (VEGF) transfected ADSCs secreted biologically active VEGF on scaffolds, (iii) in-vivo implantation of PLAGA scaffolds containing transfected ADSCs and endothelial cells showed a significantly improved vascular ingrowth.