Modeling Cardiovascular Development: New Approaches are Making In Vitro En Vogue

Abstract

In vitro models have proven themselves to be powerful allies with in vivo models for the dissection of the molecular mechanisms of cardiovascular development. The purpose of this manuscript is to review the advances that have enabled the creation of a new generation of in vitro models. These advances include the advent of new biomaterials and cell scaffolds that have provided the opportunity to design niches where developmental processes can occur under controlled, in vitro conditions. The engineering of biomaterials, along with new imaging capabilities, are being applied to important developmental questions. These interdisciplinary approaches promise to accelerate the identification of the molecular processes that regulate the cell-cell and cell-extracellular matrix (ECM) interactions that occur during the development of cardiac tissues. These new models not only offer the opportunity to test molecular mechanisms but also provide morphogenetic assays where the development of functional cardiovascular tissues can be achieved. The advent of these technologies is far reaching: from the ability to engineer functional cardiovascular tissues to the rational implantation of cell therapies for cardiovascular disease.Key Words: Cardiac development, tissue engineering, in vitro models. PURPOSE AND SCOPEIn recent years, a great deal of progress has been made in determining many of the factors that regulate cardiovascular development. This progress has been accomplished through the use of both in vivo and in vitro models. Although in vivo models are critically important, their inherent complexity can confound experimental analysis. On the other hand, the advantage of in vitro models lies largely in the ability to control the number of experimental variables. Their application can be limited, however. These limitations are dependent on the fidelity to which they model the intended process. Recently described models presented in this review offer the ability to extend the applicability of in vitro models by making them more relevant to cardiovascular development in vivo.For the purposes of this review, in vitro development is defined as development that takes place under artificial conditions. This could be interpreted to include transgenic and knockout approaches; however, this review will exclude those techniques in which development occurs in utero. Likewise, models using Xenopus laevis and Zebrafish will not be discussed in detail. These models have added tremendously to the body of knowledge of cardiovascular biology but do not appear to require complex culturing techniques that will be discussed here. Why developing amniotes require specialized culture conditions is an intriguing question, but will not be addressed here. Specifically, we will focus on emerging in vitro models and how they can be used to investigate fundamental questions of cardiovascular development including coronary vessel development, the role of physical forces, fibroblast/myocyte interactions and late valve formation.This review is divided into thr...