Preprint Article Version 1 This version is not peer-reviewed

Collagen I Microfiber Promote Brain Capillary Network Formation in Three-Dimensional Blood-Brain Barrier-Microphysiological Systems

Kimiko Nakayama-Kitamura
ORCID logo ,
Yukari Shigemoto-Mogami
,
Marie Piantino
,
Yasuhiro Naka
,
Asuka Yamada
,
Shiro Kitano
,
Tomomi Furihata
ORCID logo ,
Michiya Matsusaki
ORCID logo ,
Kaoru Sato
*
Version 1 : Received: 27 September 2024 / Approved: 27 September 2024 / Online: 29 September 2024 (04:08:50 CEST)

How to cite: Nakayama-Kitamura, K.; Shigemoto-Mogami, Y.; Piantino, M.; Naka, Y.; Yamada, A.; Kitano, S.; Furihata, T.; Matsusaki, M.; Sato, K. Collagen I Microfiber Promote Brain Capillary Network Formation in Three-Dimensional Blood-Brain Barrier-Microphysiological Systems. Preprints 2024, 2024092209. https://doi.org/10.20944/preprints202409.2209.v1 Nakayama-Kitamura, K.; Shigemoto-Mogami, Y.; Piantino, M.; Naka, Y.; Yamada, A.; Kitano, S.; Furihata, T.; Matsusaki, M.; Sato, K. Collagen I Microfiber Promote Brain Capillary Network Formation in Three-Dimensional Blood-Brain Barrier-Microphysiological Systems. Preprints 2024, 2024092209. https://doi.org/10.20944/preprints202409.2209.v1

Abstract

The blood-brain barrier (BBB) strictly regulates the penetration of substances into the brain, which, although important for maintaining brain homeostasis, may delay drug development because of the difficulties in predicting pharmacokinetics/pharmacodynamics (PKPD), toxicokinetics/toxicodynamics (TKTD), toxicity, safety, and efficacy in the central nervous system (CNS). Moreover, BBB functional proteins show species differences; therefore, humanized in vitro BBB models are urgently needed to improve the predictability of preclinical studies. Recently, international trends in the 3Rs in animal experiments and the approval of the FDA Modernization Act 2.0 have accelerated the application of microphysiological systems (MPSs) in preclinical studies, and in vitro BBB models have become synonymous with BBB-MPSs. Recently, we developed an industrialized humanized BBB-MPS, BBB-NET. In our previous report, we reproduced transferrin receptor (TfR)-mediated transcytosis with high efficiency and robustness with hydrogels that include fibrin and collagen I microfibers (CMFs). Herein, we investigated how adding CMFs to the fibrin gel benefits BBB-NETs, showed that CMFs accelerated capillary network formation and maturation by promoting astrocyte (AC) survival, and clarified that integrin 1 is involved in the mechanism of CMFs. Our data suggest that quality control (QC) of CMFs is important for ensuring the stable production of BBB-NETs.

Keywords

blood-brain barrier (BBB); microphysiological system (MPS); collagen I microfiber (CMF); integrin; humanized model

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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