2012
DOI: 10.1126/scitranslmed.3004804
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Dynamic Microenvironments: The Fourth Dimension

Abstract: The extracellular space, or cell microenvironment, choreographs cell behavior through myriad controlled signals, and aberrant cues can result in dysfunction and disease. For functional studies of human cell biology or expansion and delivery of cells for therapeutic purposes, scientists must decipher this intricate map of microenvironment biology and develop ways to mimic these functions in vitro. In this Perspective, we describe technologies for four-dimensional (4D) biology: cell-laden matrices engineered to … Show more

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Cited by 148 publications
(122 citation statements)
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“…As spheroids consist of a distinct construction (hypoxic core enriched with a quiescent viable central zone with tendency to necrosis, as well as the outer proliferating zone) the rates of proliferation of several tumor cell lines might be reduced compared to its behavior in a 2D model (45). The underlying mechanisms include different oxygen/nutrient/growth factor gradients, stromal cell and extracellular matrix influence (30,(55)(56)(57)(58). However, 3D models represent the most promising tumor model before moving to expensive animal models that remain the most predicting models for preclinical drug testing (59).…”
Section: Anticancer Researchmentioning
confidence: 99%
“…As spheroids consist of a distinct construction (hypoxic core enriched with a quiescent viable central zone with tendency to necrosis, as well as the outer proliferating zone) the rates of proliferation of several tumor cell lines might be reduced compared to its behavior in a 2D model (45). The underlying mechanisms include different oxygen/nutrient/growth factor gradients, stromal cell and extracellular matrix influence (30,(55)(56)(57)(58). However, 3D models represent the most promising tumor model before moving to expensive animal models that remain the most predicting models for preclinical drug testing (59).…”
Section: Anticancer Researchmentioning
confidence: 99%
“…Click chemistry has recently emerged as an alternative approach to synthesize covalently crosslinked hydrogels with high chemoselectivity and fast reaction rates in complex aqueous media, at physiologically relevant pH and temperature ranges both in vitro and in vivo [23]. Recent findings have established a set of bioorthogonal click reactions that do not require the cytotoxic copper catalyst used in early reports.…”
Section: Introductionmentioning
confidence: 99%
“…Nejčastěji se používají přírodní hydrogely, jako je Matrigel (gelová směs proteinů extracelulární matrix) nebo kolagen, které současně simulují přirozené vytváření spojů mezi nádorovými buň-kami a ECM, která rovněž významně ovlivňuje buněčnou signalizaci [44,45]. Nádorové buňky kultivované ve 2D podmínkách jsou přichyceny k plastovému podkladu, vykazují stejnou míru proliferace, jsou rovnoměrně vystavené působení látek z vnějšího prostředí a interagují se sousedními buňkami pouze malou částí svého povrchu.…”
Section: D In Vitro Modelyunclassified