Tissue surface tensions guide in vitro self‐assembly of rodent pancreatic islet cells

Jia, Dongxuan; DaJusta, Daniel; Foty, Ramsey A.

doi:10.1002/dvdy.21207

Cited by 42 publications

(32 citation statements)

References 49 publications

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“…Spatially arranged clusters of different cell types are reminiscent of endocrine tissue architecture in vivo. For instance, four cell types, including alpha and beta cells, are clustered within functionally distinct regions in the Islets of Langerhans (Jia et al, 2007). Using cells differentiated from stem cells, it should be possible to reproduce the optimal arrangement of cell types within a mixed microtissue for use in pancreatic replacement therapy.…”

Section: Discussionmentioning

confidence: 99%

Controlling cell position in complex heterotypic 3D microtissues by tissue fusion

Rago

Dean

Morgan

2008

Biotech & Bioengineering

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Tissue fusion and cell sorting are processes fundamental to developmental biology with applications in tissue engineering. We have designed a fusion assay to investigate the factors governing the fusion of microtissues and the cell sorting that occurs after fusion. Normal human fibroblast (NHF) spheroids were self-assembled and cultured for 1, 4, or 7 days, then combined in trough shaped recesses. Over a 24-h period the spheroids fused to become a rod shaped microtissue and the kinetics and extent of fusion could be quantified by assessing rod contraction. By varying the amount of spheroid culture time prior to fusion (1-7 days), the rate of fusion, the coherence of the building units (as measured by fusion angle) and the steady state length of the structure could be easily controlled. Longer pre-culture times for the spheroids resulted in slower fusion, less coherence and increased length of rod microtissues. The fusion kinetics and steady length of rods formed by smaller versus larger spheroids ( approximately 100 vs. 300 microm diameter) were indistinguishable, even though smaller spheroids had twice the surface area and greater numbers of contacts between units. Both small and large spheroids were strongly influenced by spheroid pre-culture time. Pre-culture time could also be used to control cell sorting and cell position when combinations of NHFs and H35s, a rat hepatocyte cell line, were fused to form heterotypic microtissues. Control of fusion and cell position are important parameters for creating functional heterotypic microtissues as well as the use of microtissues as building units to create larger tissue structures.

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Section: Discussionmentioning

confidence: 99%

Controlling cell position in complex heterotypic 3D microtissues by tissue fusion

Rago

Dean

Morgan

2008

Biotech & Bioengineering

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“…Space constraints prevent the discussion of several relevant systems, which can be cited here only for reference. These include the compound eye of the insect, which is treated elsewhere in this volume, many examples of cell intercalation [10], involvement of a protocadherin in zebrafish somite segmentation and movements of paraxial cells [11], establishment of the notochord-somite boundary [12], the layering of granule cell precursors and inhibitory interneurons in the developing cerebellar cortex [13], the stratification of endocrine cells in pancreatic islets [14 ], and the positioning of zebrafish germ layers (E-M Schö tz et al, unpublished).…”

Section: Introductionmentioning

confidence: 99%

Differential adhesion in morphogenesis: a modern view

Steinberg

2007

Current Opinion in Genetics & Development

347

266

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“…Spheroid formation is a typical liquid behavior. The concept of tissue liquidity has been demonstrated to play a part in a wide range of events in embryogenesis (33)(34)(35), wound healing (35), and malignancy (30,(35)(36)(37), and the underlying principle has been used to guide efforts at tissue engineering (34,35,(38)(39)(40). Embryonic tissues of avian, teleost, and amphibian origin have been shown to exhibit liquid-like behavior.…”

Section: Discussionmentioning

confidence: 99%

Lung Self-Assembly Is Modulated by Tissue Surface Tensions

Schwarz¹,

Zheng²,

Legan³

et al. 2011

Am J Respir Cell Mol Biol

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To identify cell-intrinsic properties that facilitate interaction between epithelial endodermal and mesenchymal mesodermal cells during lung morphogenesis, we developed a model of lung selfassembly that mimics fetal lung formation in structure, polarity, vasculature, and extracellular matrix expression. Three-dimensional pulmonary bodies (PBs) spontaneously self-assemble from singlecell suspensions and exhibit liquid-like properties that allow measurements of compaction rate and cohesion, and that may help to specify cellular self-organization. We hypothesized that changes in one or more of these parameters could potentially explain the lung hypoplasia associated with abnormal lung development. We examined the impact of endothelial/monocyte-activating polypeptide (EMAP) II in PBs, because EMAPII is highly expressed in lung hypoplasia. EMAPII significantly increased compaction rate and decreased overall cohesion of PBs composed of both epithelial and mesenchymal cells. Moreover, the effects of EMAPII on compaction and cohesion act exclusively through the mesenchymal cell population by interfering with fibronectin matrix assembly. We also show that EMAPII alters epithelial cell polarity and surfactant protein C expression. Our findings demonstrate, for the first time, that PBs possess liquid-like properties that can help to guide the self-assembly of fetal lungs, and that EMAPII expression can influence both mesenchymal and epithelial cells but through different molecular mechanisms.Keywords: cohesion; cell-cell interactions; polarity; extracellular matrix Early lung morphogenesis, initiated by a series of genetic cues, is characterized by the evagination of the foregut epithelium into the underlying mesoderm. Using a stereotypic pattern of reproducible budding and branching events, a tree-like system of epithelial branches gives rise to the mature lung organ. In conjunction with epithelial branching, a complex vascular tree, comprised of vessels arising from angiogenic and vasculogenic mechanisms, establishes an alveolar and vascular interface capable of oxygen exchange. The proximity and interdependence of the distal lung alveoli and vasculature for progression of normal development underscore the importance of an adhesion-based mechanism capable of mediating these cellular interactions. For example, vascular overabundance in lungspecific surfactant protein C (SPC) promoter vascular endothelial growth factor transgenic mice is associated with abnormal branching morphogenesis and inhibition of type I cell differentiation (1). Antiangiogenic proteins also influence distal lung morphogenesis. For instance, endothelial/monocyte-activating polypeptide (EMAP) II has been shown to markedly decrease lung vasculature, induce distal lung hypoplasia, and inhibit distal epithelial cell differentiation in a fetal lung allograft model (2). Conversely, disruption of a gene associated with epithelial structural maturation, such as transforming growth factor-b1, results in vascular malformations in conjunction with the arrest of...

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Tissue surface tensions guide in vitro self‐assembly of rodent pancreatic islet cells

Cited by 42 publications

References 49 publications

Controlling cell position in complex heterotypic 3D microtissues by tissue fusion

Controlling cell position in complex heterotypic 3D microtissues by tissue fusion

Differential adhesion in morphogenesis: a modern view

Lung Self-Assembly Is Modulated by Tissue Surface Tensions

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