Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids

Tissue vasculature efficiently distributes nutrients, removes metabolites, and possesses selective cellular permeability for tissue growth and function. Engineered tissue models have been limited by small volumes, low cell densities, and invasive cell extraction due to ineffective nutrient diffusion...

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Main Authors: Mark C. Allenby, Asma Tahlawi, José C. F. Morais, Kang Li, Nicki Panoskaltsis, Athanasios Mantalaris
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/6230214
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author Mark C. Allenby
Asma Tahlawi
José C. F. Morais
Kang Li
Nicki Panoskaltsis
Athanasios Mantalaris
author_facet Mark C. Allenby
Asma Tahlawi
José C. F. Morais
Kang Li
Nicki Panoskaltsis
Athanasios Mantalaris
author_sort Mark C. Allenby
collection DOAJ
description Tissue vasculature efficiently distributes nutrients, removes metabolites, and possesses selective cellular permeability for tissue growth and function. Engineered tissue models have been limited by small volumes, low cell densities, and invasive cell extraction due to ineffective nutrient diffusion and cell-biomaterial attachment. Herein, we describe the fabrication and testing of ceramic hollow fibre membranes (HFs) able to separate red blood cells (RBCs) and mononuclear cells (MNCs) and be incorporated into 3D tissue models to improve nutrient and metabolite exchange. These HFs filtered RBCs from human umbilical cord blood (CB) suspensions of 20% RBCs to produce 90% RBC filtrate suspensions. When incorporated within 5 mL of 3D collagen-coated polyurethane porous scaffold, medium-perfused HFs maintained nontoxic glucose, lactate, pH levels, and higher cell densities over 21 days of culture in comparison to nonperfused 0.125 mL scaffolds. This hollow fibre bioreactor (HFBR) required a smaller per-cell medium requirement and operated at cell densities > 10-fold higher than current 2D methods whilst allowing for continuous cell harvest through HFs. Herein, we propose HFs to improve 3D cell culture nutrient and metabolite diffusion, increase culture volume and cell density, and continuously harvest products for translational cell therapy biomanufacturing protocols.
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spelling doaj-art-d24c312d50b640c0ac68b6d00b179b622025-02-03T05:53:46ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/62302146230214Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic OrganoidsMark C. Allenby0Asma Tahlawi1José C. F. Morais2Kang Li3Nicki Panoskaltsis4Athanasios Mantalaris5Biological Systems Engineering Laboratory, Department of Chemical Engineering, Imperial College London, London, UKBiological Systems Engineering Laboratory, Department of Chemical Engineering, Imperial College London, London, UKBiological Systems Engineering Laboratory, Department of Chemical Engineering, Imperial College London, London, UKTransport & Separation Laboratory, Department of Chemical Engineering, Imperial College London, London, UKBiological Systems Engineering Laboratory, Department of Hematology, Imperial College London, London, UKBiological Systems Engineering Laboratory, Department of Chemical Engineering, Imperial College London, London, UKTissue vasculature efficiently distributes nutrients, removes metabolites, and possesses selective cellular permeability for tissue growth and function. Engineered tissue models have been limited by small volumes, low cell densities, and invasive cell extraction due to ineffective nutrient diffusion and cell-biomaterial attachment. Herein, we describe the fabrication and testing of ceramic hollow fibre membranes (HFs) able to separate red blood cells (RBCs) and mononuclear cells (MNCs) and be incorporated into 3D tissue models to improve nutrient and metabolite exchange. These HFs filtered RBCs from human umbilical cord blood (CB) suspensions of 20% RBCs to produce 90% RBC filtrate suspensions. When incorporated within 5 mL of 3D collagen-coated polyurethane porous scaffold, medium-perfused HFs maintained nontoxic glucose, lactate, pH levels, and higher cell densities over 21 days of culture in comparison to nonperfused 0.125 mL scaffolds. This hollow fibre bioreactor (HFBR) required a smaller per-cell medium requirement and operated at cell densities > 10-fold higher than current 2D methods whilst allowing for continuous cell harvest through HFs. Herein, we propose HFs to improve 3D cell culture nutrient and metabolite diffusion, increase culture volume and cell density, and continuously harvest products for translational cell therapy biomanufacturing protocols.http://dx.doi.org/10.1155/2018/6230214
spellingShingle Mark C. Allenby
Asma Tahlawi
José C. F. Morais
Kang Li
Nicki Panoskaltsis
Athanasios Mantalaris
Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids
Stem Cells International
title Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids
title_full Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids
title_fullStr Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids
title_full_unstemmed Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids
title_short Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids
title_sort ceramic hollow fibre constructs for continuous perfusion and cell harvest from 3d hematopoietic organoids
url http://dx.doi.org/10.1155/2018/6230214
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