Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion

Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using tradition...
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Autor*in:	Bellucci, Linda [verfasserIn] Montini, Giovanni [verfasserIn] Collino, Federica [verfasserIn] Bussolati, Benedetta [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Glomerular permeability Podocytes Exosomes Mesenchymal stromal cell

Anmerkung:	© The Author(s) 2021

Übergeordnetes Werk:	Enthalten in: Tissue Engineering and Regenerative Medicine - Springer Netherlands, 2012, 18(2021), 4 vom: 27. Juli, Seite 549-560
Übergeordnetes Werk:	volume:18 ; year:2021 ; number:4 ; day:27 ; month:07 ; pages:549-560

Links:	Volltext

DOI / URN:	10.1007/s13770-021-00374-9

Katalog-ID:	SPR044718292

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allfields	10.1007/s13770-021-00374-9 doi (DE-627)SPR044718292 (SPR)s13770-021-00374-9-e DE-627 ger DE-627 rakwb eng Bellucci, Linda verfasserin aut Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. Glomerular permeability (dpeaa)DE-He213 Podocytes (dpeaa)DE-He213 Exosomes (dpeaa)DE-He213 Mesenchymal stromal cell (dpeaa)DE-He213 Montini, Giovanni verfasserin aut Collino, Federica verfasserin aut Bussolati, Benedetta verfasserin aut Enthalten in Tissue Engineering and Regenerative Medicine Springer Netherlands, 2012 18(2021), 4 vom: 27. Juli, Seite 549-560 (DE-627)SPR032345240 nnns volume:18 year:2021 number:4 day:27 month:07 pages:549-560 https://dx.doi.org/10.1007/s13770-021-00374-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_61 GBV_ILN_65 GBV_ILN_69 GBV_ILN_130 GBV_ILN_285 AR 18 2021 4 27 07 549-560
spelling	10.1007/s13770-021-00374-9 doi (DE-627)SPR044718292 (SPR)s13770-021-00374-9-e DE-627 ger DE-627 rakwb eng Bellucci, Linda verfasserin aut Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. Glomerular permeability (dpeaa)DE-He213 Podocytes (dpeaa)DE-He213 Exosomes (dpeaa)DE-He213 Mesenchymal stromal cell (dpeaa)DE-He213 Montini, Giovanni verfasserin aut Collino, Federica verfasserin aut Bussolati, Benedetta verfasserin aut Enthalten in Tissue Engineering and Regenerative Medicine Springer Netherlands, 2012 18(2021), 4 vom: 27. Juli, Seite 549-560 (DE-627)SPR032345240 nnns volume:18 year:2021 number:4 day:27 month:07 pages:549-560 https://dx.doi.org/10.1007/s13770-021-00374-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_61 GBV_ILN_65 GBV_ILN_69 GBV_ILN_130 GBV_ILN_285 AR 18 2021 4 27 07 549-560
allfields_unstemmed	10.1007/s13770-021-00374-9 doi (DE-627)SPR044718292 (SPR)s13770-021-00374-9-e DE-627 ger DE-627 rakwb eng Bellucci, Linda verfasserin aut Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. Glomerular permeability (dpeaa)DE-He213 Podocytes (dpeaa)DE-He213 Exosomes (dpeaa)DE-He213 Mesenchymal stromal cell (dpeaa)DE-He213 Montini, Giovanni verfasserin aut Collino, Federica verfasserin aut Bussolati, Benedetta verfasserin aut Enthalten in Tissue Engineering and Regenerative Medicine Springer Netherlands, 2012 18(2021), 4 vom: 27. Juli, Seite 549-560 (DE-627)SPR032345240 nnns volume:18 year:2021 number:4 day:27 month:07 pages:549-560 https://dx.doi.org/10.1007/s13770-021-00374-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_61 GBV_ILN_65 GBV_ILN_69 GBV_ILN_130 GBV_ILN_285 AR 18 2021 4 27 07 549-560
allfieldsGer	10.1007/s13770-021-00374-9 doi (DE-627)SPR044718292 (SPR)s13770-021-00374-9-e DE-627 ger DE-627 rakwb eng Bellucci, Linda verfasserin aut Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. Glomerular permeability (dpeaa)DE-He213 Podocytes (dpeaa)DE-He213 Exosomes (dpeaa)DE-He213 Mesenchymal stromal cell (dpeaa)DE-He213 Montini, Giovanni verfasserin aut Collino, Federica verfasserin aut Bussolati, Benedetta verfasserin aut Enthalten in Tissue Engineering and Regenerative Medicine Springer Netherlands, 2012 18(2021), 4 vom: 27. Juli, Seite 549-560 (DE-627)SPR032345240 nnns volume:18 year:2021 number:4 day:27 month:07 pages:549-560 https://dx.doi.org/10.1007/s13770-021-00374-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_61 GBV_ILN_65 GBV_ILN_69 GBV_ILN_130 GBV_ILN_285 AR 18 2021 4 27 07 549-560
allfieldsSound	10.1007/s13770-021-00374-9 doi (DE-627)SPR044718292 (SPR)s13770-021-00374-9-e DE-627 ger DE-627 rakwb eng Bellucci, Linda verfasserin aut Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. Glomerular permeability (dpeaa)DE-He213 Podocytes (dpeaa)DE-He213 Exosomes (dpeaa)DE-He213 Mesenchymal stromal cell (dpeaa)DE-He213 Montini, Giovanni verfasserin aut Collino, Federica verfasserin aut Bussolati, Benedetta verfasserin aut Enthalten in Tissue Engineering and Regenerative Medicine Springer Netherlands, 2012 18(2021), 4 vom: 27. Juli, Seite 549-560 (DE-627)SPR032345240 nnns volume:18 year:2021 number:4 day:27 month:07 pages:549-560 https://dx.doi.org/10.1007/s13770-021-00374-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_61 GBV_ILN_65 GBV_ILN_69 GBV_ILN_130 GBV_ILN_285 AR 18 2021 4 27 07 549-560
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topic_title	Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion Glomerular permeability (dpeaa)DE-He213 Podocytes (dpeaa)DE-He213 Exosomes (dpeaa)DE-He213 Mesenchymal stromal cell (dpeaa)DE-He213
topic	misc Glomerular permeability misc Podocytes misc Exosomes misc Mesenchymal stromal cell
topic_unstemmed	misc Glomerular permeability misc Podocytes misc Exosomes misc Mesenchymal stromal cell
topic_browse	misc Glomerular permeability misc Podocytes misc Exosomes misc Mesenchymal stromal cell
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title	Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion
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title_full	Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion
author_sort	Bellucci, Linda
journal	Tissue Engineering and Regenerative Medicine
journalStr	Tissue Engineering and Regenerative Medicine
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author_browse	Bellucci, Linda Montini, Giovanni Collino, Federica Bussolati, Benedetta
container_volume	18
format_se	Elektronische Aufsätze
author-letter	Bellucci, Linda
doi_str_mv	10.1007/s13770-021-00374-9
author2-role	verfasserin
title_sort	mesenchymal stromal cell-derived extracellular vesicles pass through the filtration barrier and protect podocytes in a 3d glomerular model under continuous perfusion
title_auth	Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion
abstract	Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. © The Author(s) 2021
abstractGer	Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. © The Author(s) 2021
abstract_unstemmed	Background: Dynamic cultures, characterized by continuous fluid reperfusion, elicit physiological responses from cultured cells. Mesenchymal stem cell-derived EVs (MSC-EVs) has been proposed as a novel approach in treating several renal diseases, including acute glomerular damage, by using traditional two-dimensional cell cultures and in vivo models. We here aimed to use a fluidic three-dimensional (3D) glomerular model to study the EV dynamics within the glomerular structure under perfusion. Methods: To this end, we set up a 3D glomerular model culturing human glomerular endothelial cells and podocytes inside a bioreactor on the opposite sides of a porous membrane coated with type IV collagen. The bioreactor was connected to a circuit that allowed fluid passage at the rate of 80 µl/min. To mimic glomerular damage, the system was subjected to doxorubicin administration in the presence of therapeutic MSC-EVs. Results: The integrity of the glomerular basal membrane in the 3D glomerulus was assessed by a permeability assay, demonstrating that the co-culture could limit the passage of albumin through the filtration barrier. In dynamic conditions, serum EVs engineered with cel-miR-39 passed through the glomerular barrier and transferred the exogenous microRNA to podocyte cell lines. Doxorubicin treatment increased podocyte apoptosis, whereas MSC-EV within the endothelial circuit protected podocytes from damage, decreasing cell death and albumin permeability. Conclusion: Using an innovative millifluidic model, able to mimic the human glomerular barrier, we were able to trace the EV passage and therapeutic effect in dynamic conditions. © The Author(s) 2021
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container_issue	4
title_short	Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion
url	https://dx.doi.org/10.1007/s13770-021-00374-9
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author2	Montini, Giovanni Collino, Federica Bussolati, Benedetta
author2Str	Montini, Giovanni Collino, Federica Bussolati, Benedetta
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up_date	2024-07-04T02:02:25.138Z
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