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Development of an In Vitro Biomimetic Peripheral Neurovascular Platform

[Image: see text] Nerves and blood vessels are present in most organs and are indispensable for their function and homeostasis. Within these organs, neurovascular (NV) tissue forms congruent patterns and establishes vital interactions. Several human pathologies, including diabetes type II, produce N...

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Autores principales: Malheiro, Afonso, Seijas-Gamardo, Adrián, Harichandan, Abhishek, Mota, Carlos, Wieringa, Paul, Moroni, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305708/
https://www.ncbi.nlm.nih.gov/pubmed/35815638
http://dx.doi.org/10.1021/acsami.2c03861
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author Malheiro, Afonso
Seijas-Gamardo, Adrián
Harichandan, Abhishek
Mota, Carlos
Wieringa, Paul
Moroni, Lorenzo
author_facet Malheiro, Afonso
Seijas-Gamardo, Adrián
Harichandan, Abhishek
Mota, Carlos
Wieringa, Paul
Moroni, Lorenzo
author_sort Malheiro, Afonso
collection PubMed
description [Image: see text] Nerves and blood vessels are present in most organs and are indispensable for their function and homeostasis. Within these organs, neurovascular (NV) tissue forms congruent patterns and establishes vital interactions. Several human pathologies, including diabetes type II, produce NV disruptions with serious consequences that are complicated to study using animal models. Complex in vitro organ platforms, with neural and vascular supply, allow the investigation of such interactions, whether in a normal or pathological context, in an affordable, simple, and direct manner. To date, a few in vitro models contain NV tissue, and most strategies report models with nonbiomimetic representations of the native environment. To this end, we have established here an NV platform that contains mature vasculature and neural tissue, composed of human microvascular endothelial cells (HMVECs), induced pluripotent stem cell (iPSCs)-derived sensory neurons, and primary rat Schwann cells (SCs) within a fibrin-embedded polymeric scaffold. First, we show that SCs can induce the formation of and stabilize vascular networks to the same degree as the traditional and more thoroughly studied human dermal fibroblasts (HDFs). We also show that through SC prepatterning, we are able to control vessel orientation. Using our NV platform, we demonstrate the concomitant formation of three-dimensional neural and vascular tissue, and the influence of different medium formulations and cell types on the NV tissue outcome. Finally, we propose a protocol to form mature NV tissue, via the integration of independent neural and vascular constituents. The platform described here provides a versatile and advanced model for in vitro research of the NV axis.
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spelling pubmed-93057082022-07-23 Development of an In Vitro Biomimetic Peripheral Neurovascular Platform Malheiro, Afonso Seijas-Gamardo, Adrián Harichandan, Abhishek Mota, Carlos Wieringa, Paul Moroni, Lorenzo ACS Appl Mater Interfaces [Image: see text] Nerves and blood vessels are present in most organs and are indispensable for their function and homeostasis. Within these organs, neurovascular (NV) tissue forms congruent patterns and establishes vital interactions. Several human pathologies, including diabetes type II, produce NV disruptions with serious consequences that are complicated to study using animal models. Complex in vitro organ platforms, with neural and vascular supply, allow the investigation of such interactions, whether in a normal or pathological context, in an affordable, simple, and direct manner. To date, a few in vitro models contain NV tissue, and most strategies report models with nonbiomimetic representations of the native environment. To this end, we have established here an NV platform that contains mature vasculature and neural tissue, composed of human microvascular endothelial cells (HMVECs), induced pluripotent stem cell (iPSCs)-derived sensory neurons, and primary rat Schwann cells (SCs) within a fibrin-embedded polymeric scaffold. First, we show that SCs can induce the formation of and stabilize vascular networks to the same degree as the traditional and more thoroughly studied human dermal fibroblasts (HDFs). We also show that through SC prepatterning, we are able to control vessel orientation. Using our NV platform, we demonstrate the concomitant formation of three-dimensional neural and vascular tissue, and the influence of different medium formulations and cell types on the NV tissue outcome. Finally, we propose a protocol to form mature NV tissue, via the integration of independent neural and vascular constituents. The platform described here provides a versatile and advanced model for in vitro research of the NV axis. American Chemical Society 2022-07-11 2022-07-20 /pmc/articles/PMC9305708/ /pubmed/35815638 http://dx.doi.org/10.1021/acsami.2c03861 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Malheiro, Afonso
Seijas-Gamardo, Adrián
Harichandan, Abhishek
Mota, Carlos
Wieringa, Paul
Moroni, Lorenzo
Development of an In Vitro Biomimetic Peripheral Neurovascular Platform
title Development of an In Vitro Biomimetic Peripheral Neurovascular Platform
title_full Development of an In Vitro Biomimetic Peripheral Neurovascular Platform
title_fullStr Development of an In Vitro Biomimetic Peripheral Neurovascular Platform
title_full_unstemmed Development of an In Vitro Biomimetic Peripheral Neurovascular Platform
title_short Development of an In Vitro Biomimetic Peripheral Neurovascular Platform
title_sort development of an in vitro biomimetic peripheral neurovascular platform
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305708/
https://www.ncbi.nlm.nih.gov/pubmed/35815638
http://dx.doi.org/10.1021/acsami.2c03861
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