Biomimetic Poly(ethylene glycol)-based Hydrogels as Cancer Model for Evaluation of Tumor Stromal Cell and Matrix Influences on Tissue Vascularization
The formation of new blood vessels around a tumor is facilitated by the complex interplay between cells in the tumor stroma and the surrounding microenvironment. Understanding this interplay and its dynamic interactions is crucial in identifying promising targets for cancer therapy. In my work, I have demonstrated the use of poly(ethylene glycol) diacrylate (PEGDA) hydrogels to recapitulate and study the tumor vascularization in 3D. I have utilized degradable PEG hydrogels to evaluate the effects of cancer associated fibroblasts (CAFs) on tumor vascularization. CAFs comprise a majority of the cells in the tumor stroma and are rich source of secreted factors. In comparison to normal lung fibroblasts (LF), CAFs accelerate the formation of new vessels. Closer examination of vessels formed by CAFs in our 3D PEG hydrogel system reveals clear differences in vessel assembly and morphology and closely represent blood vessels found in tumors in vivo. Our findings suggest that CAFs play a crucial role in enhancing tumor vascularization and subsequently direct the malignant conversion of benign tumors to metastatic cancer. My work offers insight on how the complex crosstalk established between ECs, CAFs and their surrounding ECM affects cancer progression and tumor vasculogenesis. Controlling this complex crosstalk can provide means for developing new therapies to treat cancer.
Co-culture of cells in 3D PEG hydrogels organized into tubule networks and observed via staining for DAPI (cell nuclei), CD31 (endothelial cells), and alpha SMA (LF or CAFs). Scale Bar =100 µm.
Investigating the Role of Macrophages in Vasculature
This project focuses on illuminating the role of macrophages in vasculature development. Recent in vivo work within the field has indicated that macrophages play an essential role in vasculature formation. In order better understand the role that macrophages can adopt in vasculature development, we are utilizing a PEG-based hydrogel system in order to create a 3D angiogenesis model investigating the role of macrophages on vessel formation. This work will provide insight into the juxtacrine and paracrine signaling effects that macrophages have on endothelial cells.
Additionally, through the use of our biomimetic PEG hydrogel system, we will also be able to study macrophage phenotype interactions within this 3D co-culture environment. Macrophages are known to adopt two main phenotypes depending on environmental stimuli- M1 macrophages which promote inflammation and M2 macrophages which are involved in tissue repair. Thus, the ability to control macrophage phenotype can directly influence the ability to regulate vasculature formation and even tissue regeneration. Therefore, we are also interested in probing the role of macrophage phenotypes in vasculature formation via our hydrogel system.
- Immobilization of Cell-Adhesive Laminin Peptides in Degradable PEGDA Hydrogels Influences Endothelial Cell Tubulogenesis. BioResearch Open Access. 2(4), 241-9. (2013).
- Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels. Advanced Functional Materials. 22(21), 4511 - 4518. (2012).
- Three-Dimensional Biomimetic Patterning in Hydrogels to Guide Cellular Organization. Advanced Materials. 24(17), 2344 - 2348. (2012).
- The promotion of microvasculature formation in poly(ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide. Biomaterials. 32(25), 5782 - 5789. (2011).