Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds

Wrighton, Paul J.; Kiessling, Laura L.

doi:10.1016/j.stem.2015.04.018

Cited by 9 publications

(13 citation statements)

References 11 publications

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“…(c) Ninety days after transplantation we noted that the graft created connections with mouse vessels. (Wrighton & Kiessling, 2015). In accordance with our study, Candiello et al (2018) showed hESC-PP and ECs coculture in a 3D material (Amikagel, a kind of hydrogel) leads to organization of islet-like structures in vitro.…”

Section: Formation Of Po By Integrating Multiple Derivatives Of Humsupporting

confidence: 83%

Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper

Soltanian

Ghezelayagh

Mazidi

et al. 2018

Journal Cellular Physiology

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Organoids can be regarded as a beneficial tool for discovery of new therapeutics for diabetes and/or maturation of pancreatic progenitors (PP) towards β cells. Here, we devised a strategy to enhance maturation of PP by assembly of three‐dimensional (3D) pancreatic organoids (PO) containing human embryonic stem (ES) cell derivatives including ES‐derived pancreatic duodenal homeobox 1 (PDX1) + early PP, mesenchymal stem cells, and endothelial cells at an optimized cell ratio, on Matrigel. The PO was placed in a 3D‐printed tissue trapper and heterotopically implanted into the peritoneal cavity of immunodeficient mice where it remained for 90 days. Our results indicated that, in contrast to corresponding early PP transplants, 3D PO developed more vascularization as indicated by greater area and number of vessels, a higher number of insulin‐positive cells and improvement of human C‐peptide secretions. Based on our findings, PO‐derived β cells could be considered a novel strategy to study human β‐cell development, novel therapeutics, and regenerative medicine for diabetes.

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Section: Formation Of Po By Integrating Multiple Derivatives Of Humsupporting

confidence: 83%

Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper

Soltanian

Ghezelayagh

Mazidi

et al. 2018

Journal Cellular Physiology

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“…An exciting new area of research is related to the in vitro generation of organ-analogous structures called organoids 4 , 29 , 30 . This research has focused mainly on the molecular manipulation of homogenous cell populations and mechanical inputs are just starting to be considered in the field 29 , 30 . As our findings reveal that proper morphogenesis requires mechanical interaction between different tissues, we anticipate that the consideration of mechanical signals in the organoid field will increase the success of ex vivo engineered tissues.…”

mentioning

confidence: 99%

Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo

Barriga

Franze

Charras

et al. 2018

Nature

462

406

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Collective cell migration (CCM) is essential for morphogenesis, tissue remodelling, and cancer invasion1,2. In vivo, groups of cells move in an orchestrated way through tissues. This movement requires forces and involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in CCM is comparatively well understood1,2, how tissue mechanics influence CCM in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion3. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiated an epithelial-to-mesenchymal transition (EMT) in neural crest cells and triggered their collective migration. To detect changes in their mechanical environment, neural crest use integrin/vinculin/talin-mediated mechanosensing. By performing mechanical and molecular manipulations, we showed that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrated that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results unveil a novel role for mesodermal convergent extension as a mechanical coordinator of morphogenesis, and thus reveal a new link between two apparently unconnected processes, gastrulation and neural crest migration, via changes in tissue mechanics. Overall, we provide the first demonstration that changes in substrate stiffness can trigger CCM by promoting EMT in vivo. More broadly, our results raise the exciting idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis4.

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“…These dynamic, reciprocal cell–cell interactions have been harnessed to create a “kidney in a dish” by cellular self‐assembly, which has been shown to reproduce some organ functionality . To realize a clinically transplantable kidney, however, the inter‐related issues of vascularization, mass transfer of nutrients and adequate size and function of the organ must be addressed . Decellularized cadaveric kidney has been suggested as the ideal scaffold to provide structural and biochemical cues to promote cellular self‐assembly .…”

Section: Discussionmentioning

confidence: 99%

“…However, these organoids are typically much smaller than the native human organ and the implantation of large numbers of these small organoids to achieve sufficient function in human patients may not be clinically practical. It has been proposed that an alternative approach would be to utilize ECM scaffolds from decellularized cadaveric organs, which can drive cellular self‐assembly and recapitulate organ function …”

Section: Introductionmentioning

confidence: 99%

Functional Kidney Bioengineering with Pluripotent Stem‐Cell‐Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds

Narayanan

Leong

et al. 2016

Adv Healthcare Materials

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Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney.

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Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds

Cited by 9 publications

References 11 publications

Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper

Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper

Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo

Functional Kidney Bioengineering with Pluripotent Stem‐Cell‐Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds

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