A high-throughput in vitro ring assay for vasoactivity using magnetic 3D bioprinting

Tseng, Hubert; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Shen, Tsaiwei; Hebel, Chris; Barthlow, Herbert; Wagoner, Matthew P.; Souza, Glauco R.

doi:10.1038/srep30640

Cited by 54 publications

(40 citation statements)

References 38 publications

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“…Using human PASMC from normal areas of resected cancer tissue, we demonstrate that MMW and LMW hyaluronan fragments lead to increased proliferation of PASMC that is inhibited by fasudil, a Rho kinase inhibitor (Figure A); no significant differences were seen in cytotoxicity between treatment groups (Figure B). We next examined the capacity of these cells to migrate using a 3D cell culture protocol (Tseng et al, ). In these experiments, we report reduced cell migration in PASMC following treatment with LMW‐HA and ULMW‐HA that was reversed following treatment with Fasudil (Figure C).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis

Collum

Chen

Hernandez

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEGroup III pulmonary hypertension (PH) is a highly lethal and widespread lung disorder that is a common complication in idiopathic pulmonary fibrosis (IPF) where it is considered to be the single most significant predictor of mortality. While increased levels of hyaluronan have been observed in IPF patients, hyaluronan-mediated vascular remodelling and the hyaluronanmediated mechanisms promoting PH associated with IPF are not fully understood. EXPERIMENTAL APPROACHExplanted lung tissue from patients with IPF with and without a diagnosis of PH was used to identify increased levels of hyaluronan. In addition, an experimental model of lung fibrosis and PH was used to test the capacity of 4-methylumbeliferone (4MU), a hyaluronan synthase inhibitor to attenuate PH. Human pulmonary artery smooth muscle cells (PASMC) were used to identify the hyaluronan-specific mechanisms that lead to the development of PH associated with lung fibrosis. KEY RESULTSIn patients with IPF and PH, increased levels of hyaluronan and expression of hyaluronan synthase genes are present. Interestingly, we also report increased levels of hyaluronidases in patients with IPF and IPF with PH. Remarkably, our data also show that 4MU is able to inhibit PH in our model either prophylactically or therapeutically, without affecting fibrosis. Studies to determine the hyaluronan-specific mechanisms revealed that hyaluronan fragments result in increased PASMC stiffness and proliferation but reduced cell motility in a RhoA-dependent manner. CONCLUSIONS AND IMPLICATIONSTaken together, our results show evidence of a unique mechanism contributing to PH in the context of lung fibrosis. Abbreviations4MU, 4-methylumbelliferone; GEFT, guanine nucleotide exchange factor 25; HABP2, hyaluronan-binding protein 2; HAS, hyaluronan synthase; HYAL, hyaluronidase; IF, immunofluorescence; IHC, immunohistochemistry; IPF, idiopathic pulmonary fibrosis; LVSP, left ventricle systolic pressure; mPAP, mean pulmonary arterial pressure; PASMC, pulmonary artery smooth muscle cell; PH, pulmonary hypertension; RVH, right ventricle hypertrophy; RVSP, right ventricle systolic pressure; αSMA, α-smooth muscle actin

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Section: Resultsmentioning

confidence: 99%

Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis

Collum

Chen

Hernandez

et al. 2017

British J Pharmacology

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“…In order to understand how the nanoparticles would penetrate in solid tumors such as that of pancreatic cancer, we grew 3D spheroidal cultures of MIA PaCa‐2 cells and treated them with Alexa Fluor 647–labeled nanoparticles composed of PG‐ co ‐PCL‐DB ( 4 ). A spheroid culture mimics native cellular environments and has been extensively used as a model system by Souza et al and other research groups to study various cancer types, drug screening, effect of metabolic inhibitors, in vitro assays, and 3D bio‐printing . We investigated the spheroid across the z ‐axis at every 10‐µm thickness (starting from the surface) for the dye fluorescence co‐localized with DAPI‐treated nuclei of pancreatic cancer cells ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

Dendritic Polyglycerol‐Derived Nano‐Architectures as Delivery Platforms of Gemcitabine for Pancreatic Cancer

Ray¹,

Ferraro

Haag

et al. 2019

Macromolecular Bioscience

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Dendritic polyglycerol‐co‐polycaprolactone (PG‐co‐PCL)‐derived block copolymers are synthesized and explored as nanoscale drug delivery platforms for a chemotherapeutic agent, gemcitabine (GEM), which is the cornerstone of therapy for pancreatic ductal adenocarcinoma (PDAC). Current treatment strategies with GEM result in suboptimal therapeutic outcome owing to microenvironmental resistance and rapid metabolic degradation of GEM. To address these challenges, physicochemical and cell‐biological properties of both covalently conjugated and non‐covalently stabilized variants of GEM‐containing PG‐co‐PCL architectures have been evaluated. Self‐assembly behavior, drug loading and release capacity, cytotoxicity, and cellular uptake properties of these constructs in monolayer and in spheroid cultures of PDAC cells are investigated. To realize the covalently conjugated carrier systems, GEM, in conjunction with a tertiary amine, is attached to the polycarbonate block grafted from the PG‐co‐PCL core. It is observed that pH‐dependent ionization properties of these amine side‐chains direct the formation of self‐assembly of block copolymers in the form of nanoparticles. For non‐covalent encapsulation, a facile “solvent‐shifting” technique is adopted. Fabrication techniques are found to control colloidal and cellular properties of GEM‐loaded nanoconstructs. The feasibility and potential of these newly developed architectures for designing carrier systems for GEM to achieve augmented prognosis for pancreatic cancer are reported.

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“…So far this technique has shown itself to be more eligible for the patterning of planar microstructures rather than larger and freestanding objects. Another layer-wise fabrication method that is just emerging is magnetic bioprinting [13], where a magnetic field is applied in order to rapidly organize cells in an arbitrary way.…”

Section: Layer-wise Bioprintingmentioning

confidence: 99%

3D bioprinting of cell-laden hydrogels for advanced tissue engineering

Blaeser

Campos

Fischer

2017

Current Opinion in Biomedical Engineering

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A high-throughput in vitro ring assay for vasoactivity using magnetic 3D bioprinting

Cited by 54 publications

References 38 publications

Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis

Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis

Dendritic Polyglycerol‐Derived Nano‐Architectures as Delivery Platforms of Gemcitabine for Pancreatic Cancer

3D bioprinting of cell-laden hydrogels for advanced tissue engineering

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