A Novel Ex Vivo Tumor Spheroid-Tissue Model for Investigating Microvascular Remodeling and Lymphatic Blood Vessel Plasticity.

Biomimetic tumor microenvironment models bridge the gap between in vitro and in vivo systems and serve as a useful way to address the modeling challenge of how to recreate the cell and system complexity associated with real tissues. Our laboratory has developed an ex vivo rat mesentery culture model, which allows for simultaneous investigation of blood and lymphatic microvascular network remodeling in an intact tissue environment. Given that angiogenesis and lymphangiogenesis are key contributors to the progression of cancer, the objective of this study was to combine tissue and tumor spheroid culture methods to establish a novel ex vivo tumor spheroid-tissue model by verifying its use for evaluating the effects of cancer cell behavior on the local microvascular environment.

Time-Lapse Observation of Cell Dynamics During Angiogenesis Using the Rat Mesentery Culture Model.

The ability to track cells and their interactions with other cells during physiological processes offers a powerful tool for scientific discovery. An ex vivo model that enables real-time investigation of cell migration during angiogenesis in adult microvascular networks would enable observation of endothelial cell dynamics during capillary sprouting. Angiogenesis is defined as the growth of new blood vessels from existing ones and involves multiple cell types including endothelial cells, pericytes, and interstitial cells.

Lymphatic/blood vessel plasticity: motivation for a future research area based on present and past observations.

The lymphatic system plays a significant role in homeostasis and drainage of excess fluid back into venous circulation. Lymphatics are also associated with a number of diseases including lymphedema, tumor metastasis, and various lymphatic malformations. Emerging evidence suggests that lymphatics might have a bigger connection to the blood vascular system than originally presumed.

The Microvascular-Lymphatic Interface and Tissue Homeostasis: Critical Questions That Challenge Current Understanding.

Lymphatic and blood microvascular networks play critical roles in the clearance of excess fluid from local tissue spaces. Given the importance of these dynamics in inflammation, tumor metastasis, and lymphedema, understanding the coordinated function and remodeling between lymphatic and blood vessels in adult tissues is necessary. Knowledge gaps exist because the functions of these two systems are typically considered separately.

A Challenge for Engineering Biomimetic Microvascular Models: How do we Incorporate the Physiology?

The gap between and assays has inspired biomimetic model development. Tissue engineered models that attempt to mimic the complexity of microvascular networks have emerged as tools for investigating cell-cell and cell-environment interactions that may be not easily viewed . A key challenge in model development, however, is determining how to recreate the multi-cell/system functional complexity of a real network environment that integrates endothelial cells, smooth muscle cells, vascular pericytes, lymphatics, nerves, fluid flow, extracellular matrix, and inflammatory cells.

Viewing stromal vascular fraction de novo vessel formation and association with host microvasculature using the rat mesentery culture model.

Objective: The objective of the study is to demonstrate the innovation and utility of mesenteric tissue culture for discovering the microvascular growth dynamics associated with adipose-derived stromal vascular fraction (SVF) transplantation. Understanding how SVF cells contribute to de novo vessel growth (i.e.

A Novel ex vivo Method for Investigating Vascularization of Transplanted Islets.

Revascularization of transplanted pancreatic islets is critical for survival and treatment of type 1 diabetes. Questions concerning how islets influence local microvascular networks and how networks form connections with islets remain understudied and motivate the need for new models that mimic the complexity of real tissue. Recently, our laboratory established the rat mesentery culture model as a tool to investigate cell dynamics involved in microvascular growth.

An Ex Vivo Tissue Culture Method for Discovering Cell Dynamics Involved in Stromal Vascular Fraction Vasculogenesis Using the Mouse Mesentery.

Stromal vascular fraction (SVF), isolated from adipose tissue, identifies as a rich cell source comprised of endothelial cells, endothelial progenitor cells, pericytes, smooth muscle cells, fibroblasts, and immune cells. SVF represents a promising therapeutic heterogonous cell source for growing new blood microvessels due to its rich niche of cells. However, the spatiotemporal dynamics of SVF within living tissues remain largely unknown.

Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids.

Epithelial organoids derived from human donor tissues are important tools in fields ranging from regenerative medicine to drug discovery. Organoid culture requires expansion of stem/progenitor cells in Matrigel, a tumor-derived extracellular matrix (ECM). An alternative completely synthetic ECM could improve reproducibility, clarify mechanistic phenomena, and enable human implantation of organoids.