Capturing complex 3D tissue physiology in vitro

FeatureAn architectural or

compositional component of a

scaffold that delineates a

distinct, defined region. For

example, features in a scaffold

with a honeycomb architecture

would include: the walls, the

hexagonal channels and the

overall shape.Tissue engineering is the process of creating functional 3D

tissues using cells combined with scaffolds or devices that

facilitate cell growth, organization and differentiation. The

field of tissue engineering is at a crossroads. Straight ahead

lies the arduous path to successful clinical therapies for

replacing human heart, liver, cartilage and other tissues

a road that is arguably longer and more challenging

than it seemed about two decades ago when the field

sprang to life, as fewer than 10 products have made it to

the clinic so far1. The side road, for now less travelled, leads

to engineered tissue and organ mimics that will never be

implanted directly into patients, but will instead be used to

transform the way we study human tissue physiology and

pathophysiology in vitro. Indeed, it might decrease the

need for organ transplants by enabling the development

of therapies that prevent or cure underlying diseases2,3.Several related factors are driving the field towards

the creation of accessible in vitro 3D tissue models. One is the

need for in vitro models that are based on human cells.

Although animal models can capture important facets of

human responses, they fail to capture others. For example,

many pathogens are species specific (for example, hepatitis C), and a leading cause for the failure of new drugs in clinical trials is liver toxicity that was not predicted by animal

or in vitro models4. And, although significant progress

has been made in humanizing mice by transplanting

human cells5,6, such models are currently challenging and

expensive to adopt for routine use in an assay format. Furthermore, fundamental differences in telomerase

regulation between rodents and humans7 have raised

questions regarding the relevance of transgenic and

inducible mouse cancer models, and incompatibilities

between certain rodent and human cytokines cast

uncertainty on human tumour xenograft models. The

development of tissue and quasi-organ in vitro models that are based on human cells therefore provides a

potential bridge for the gap between animal models and

human studies, to help understand the basic mechanisms

of human disease. Furthermore, due to the ~US$1...