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Scaffold-based lung tumor culture on porous PLGA microparticle substrates

Scaffold-based cancer cell culture techniques have been gaining prominence especially in the last two decades. These techniques can potentially overcome some of the limitations of current three-dimensional cell culture methods, such as uneven cell distribution, inadequate nutrient diffusion, and unc...

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Published in:PloS one 2019-05, Vol.14 (5), p.e0217640-e0217640
Main Authors: Kuriakose, Aneetta E, Hu, Wenjing, Nguyen, Kytai T, Menon, Jyothi U
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Hu, Wenjing
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Menon, Jyothi U
description Scaffold-based cancer cell culture techniques have been gaining prominence especially in the last two decades. These techniques can potentially overcome some of the limitations of current three-dimensional cell culture methods, such as uneven cell distribution, inadequate nutrient diffusion, and uncontrollable size of cell aggregates. Porous scaffolds can provide a convenient support for cell attachment, proliferation and migration, and also allows diffusion of oxygen, nutrients and waste. In this paper, a comparative study was done on porous poly (lactic-co-glycolic acid) (PLGA) microparticles prepared using three porogens-gelatin, sodium bicarbonate (SBC) or novel poly N-isopropylacrylamide [PNIPAAm] particles, as substrates for lung cancer cell culture. These fibronectin-coated, stable particles (19-42 μm) supported A549 cell attachment at an optimal cell seeding density of 250,000 cells/ mg of particles. PLGA-SBC porous particles had comparatively larger, more interconnected pores, and favored greater cell proliferation up to 9 days than their counterparts. This indicates that pore diameters and interconnectivity have direct implications on scaffold-based cell culture compared to substrates with minimally interconnected pores (PLGA-gelatin) or pores of uniform sizes (PLGA-PMPs). Therefore, PLGA-SBC-based tumor models were chosen for preliminary drug screening studies. The greater drug resistance observed in the lung cancer cells grown on porous particles compared to conventional cell monolayers agrees with previous literature, and indicates that the PLGA-SBC porous microparticle substrates are promising for in vitro tumor or tissue development.
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There are no patents, or products in development or in the market to declare.</notes><abstract>Scaffold-based cancer cell culture techniques have been gaining prominence especially in the last two decades. These techniques can potentially overcome some of the limitations of current three-dimensional cell culture methods, such as uneven cell distribution, inadequate nutrient diffusion, and uncontrollable size of cell aggregates. Porous scaffolds can provide a convenient support for cell attachment, proliferation and migration, and also allows diffusion of oxygen, nutrients and waste. In this paper, a comparative study was done on porous poly (lactic-co-glycolic acid) (PLGA) microparticles prepared using three porogens-gelatin, sodium bicarbonate (SBC) or novel poly N-isopropylacrylamide [PNIPAAm] particles, as substrates for lung cancer cell culture. These fibronectin-coated, stable particles (19-42 μm) supported A549 cell attachment at an optimal cell seeding density of 250,000 cells/ mg of particles. PLGA-SBC porous particles had comparatively larger, more interconnected pores, and favored greater cell proliferation up to 9 days than their counterparts. This indicates that pore diameters and interconnectivity have direct implications on scaffold-based cell culture compared to substrates with minimally interconnected pores (PLGA-gelatin) or pores of uniform sizes (PLGA-PMPs). Therefore, PLGA-SBC-based tumor models were chosen for preliminary drug screening studies. The greater drug resistance observed in the lung cancer cells grown on porous particles compared to conventional cell monolayers agrees with previous literature, and indicates that the PLGA-SBC porous microparticle substrates are promising for in vitro tumor or tissue development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31150477</pmid><doi>10.1371/journal.pone.0217640</doi><orcidid>https://orcid.org/0000-0002-0762-3513</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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1932-6203
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subjects Bioengineering
Biology and Life Sciences
Biomedical engineering
Biotechnology
Cell adhesion
Cell Adhesion - drug effects
Cell Count
Cell culture
Cell Culture Techniques
Cell death
Cell migration
Cell proliferation
Cell Proliferation - drug effects
Cell size
Cell Survival - drug effects
Cell-Derived Microparticles - drug effects
Comparative studies
Culture techniques
Diffusion
Drug Evaluation, Preclinical - methods
Drug resistance
Drug Resistance, Neoplasm - drug effects
Drug screening
Extracellular matrix
Fibronectin
Gelatin
Gelatin - chemistry
Gelatin - pharmacology
Glycolic acid
Humans
Isopropylacrylamide
Lung cancer
Lung diseases
Lung Neoplasms - drug therapy
Lung Neoplasms - pathology
Medicine and Health Sciences
Metabolism
Methods
Microparticles
Nutrients
Oxygen
Polylactic acid
Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology
Polylactide-co-glycolide
Pores
Porosity
Research and Analysis Methods
Scaffolds
Sodium
Sodium bicarbonate
Spheroids
Substrates
Tissue Engineering
Tissue Scaffolds - chemistry
Tumors
title Scaffold-based lung tumor culture on porous PLGA microparticle substrates
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