Development of an In Vitro Biomimetic Peripheral Neurovascular Platform

Afonso Malheiro, Adrián Seijas-Gamardo, Abhishek Harichandan, Carlos Mota, Paul Wieringa, Lorenzo Moroni*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)31567-31585
Number of pages19
JournalACS Applied Materials & Interfaces
Volume14
Issue number28
Early online date10 Jul 2022
DOIs
Publication statusPublished - 20 Jul 2022

Keywords

  • ANGIOGENESIS
  • ARTERIAL DIFFERENTIATION
  • BLOOD-VESSELS
  • ENDOTHELIAL-CELL
  • MICROFLUIDIC MODEL
  • NERVE
  • PROLIFERATION
  • SCHWANN-CELLS
  • STEM-CELLS
  • Schwann cells
  • VEGF-A
  • endothelial cells
  • in vitro model
  • neurons
  • neurovascular interactions
  • three-dimensional

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