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2014 ; 239
(9
): 1264-71
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Tissue-engineered microenvironment systems for modeling human vasculature
#MMPMID25030480
Tourovskaia A
; Fauver M
; Kramer G
; Simonson S
; Neumann T
Exp Biol Med (Maywood)
2014[Sep]; 239
(9
): 1264-71
PMID25030480
show ga
The high attrition rate of drug candidates late in the development process has
led to an increasing demand for test assays that predict clinical outcome better
than conventional 2D cell culture systems and animal models. Government agencies,
the military, and the pharmaceutical industry have started initiatives for the
development of novel in-vitro systems that recapitulate functional units of human
tissues and organs. There is growing evidence that 3D cell arrangement,
co-culture of different cell types, and physico-chemical cues lead to improved
predictive power. A key element of all tissue microenvironments is the
vasculature. Beyond transporting blood the microvasculature assumes important
organ-specific functions. It is also involved in pathologic conditions, such as
inflammation, tumor growth, metastasis, and degenerative diseases. To provide a
tool for modeling this important feature of human tissue microenvironments, we
developed a microfluidic chip for creating tissue-engineered microenvironment
systems (TEMS) composed of tubular cell structures. Our chip design encompasses a
small chamber that is filled with an extracellular matrix (ECM) surrounding one
or more tubular channels. Endothelial cells (ECs) seeded into the channels adhere
to the ECM walls and grow into perfusable tubular tissue structures that are
fluidically connected to upstream and downstream fluid channels in the chip.
Using these chips we created models of angiogenesis, the blood-brain barrier
(BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true
angiogenesis, in which sprouting occurs from a "parent" vessel in response to a
gradient of growth factors. Our BBB model is composed of a microvessel generated
from brain-specific ECs within an ECM populated with astrocytes and pericytes.
Our tumor-cell extravasation model can be utilized to visualize and measure
tumor-cell migration through vessel walls into the surrounding matrix. The
described technology can be used to create TEMS that recapitulate structural,
functional, and physico-chemical elements of vascularized human tissue
microenvironments in vitro.
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