Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2023; 15(6): 632-653
Published online Jun 26, 2023. doi: 10.4252/wjsc.v15.i6.632
Current overview of induced pluripotent stem cell-based blood-brain barrier-on-a-chip
Arielly da Hora Alves, Mariana Penteado Nucci, Nicole Mastandrea Ennes do Valle, Juliana Morais Missina, Javier Bustamante Mamani, Gabriel Nery Albuquerque Rego, Olivia Furiama Metropolo Dias, Murilo Montenegro Garrigós, Fernando Anselmo de Oliveira, Lionel Fernel Gamarra
Arielly da Hora Alves, Mariana Penteado Nucci, Nicole Mastandrea Ennes do Valle, Juliana Morais Missina, Javier Bustamante Mamani, Gabriel Nery Albuquerque Rego, Olivia Furiama Metropolo Dias, Murilo Montenegro Garrigós, Fernando Anselmo de Oliveira, Lionel Fernel Gamarra, Hospital Israelita Albert Einstein, São Paulo 05529-060, São Paulo, Brazil
Mariana Penteado Nucci, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, São Paulo, Brazil
Author contributions: Alves ADH, Nucci MP, Ennes do Valle NM, Missina JM, and Gamarra LF conceived and designed this study; Alves ADH, Nucci MP, Ennes do Valle NM, Rego GNA, and Gamarra LF performed the literature review; Alves ADH, Nucci MP, Ennes do Valle NM, Rego GNA, Mamani JB, and Missina JM performed the data extraction and critical review; Alves ADH, Nucci MP, Ennes do Valle NM, Missina JM, de Oliveira FA, and Mamani JB interpreted and analyzed the collected data; Alves ADH, Nucci MP, Ennes do Valle NM, Missina JM, Dias OFM, Garrigós MM, and Gamarra LF wrote this review; All authors reviewed and approved the final manuscript as submitted.
Supported by CNPq, Nos. 308901/2020-7 and 400856/2016-6; FAPESP, Nos. 2019/21070-3, 2017/17868-4, and 2016/21470-3; SisNANO 2.0/MCTIC, No. 442539/2019-3; and the National Institute of Science and Technology Complex Fluids, INCT-FCx.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA guidelines, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lionel Fernel Gamarra, PhD, Academic Research, Professor, Research Associate, Teacher, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/701, Morumbi, São Paulo 05529-060, São Paulo, Brazil. lgamarra@einstein.br
Received: February 15, 2023
Peer-review started: February 15, 2023
First decision: April 10, 2023
Revised: April 10, 2023
Accepted: May 8, 2023
Article in press: May 8, 2023
Published online: June 26, 2023
ARTICLE HIGHLIGHTS
Research background

Induced pluripotent stem cells (iPSCs) offer a potential alternative to building blood-brain barrier (BBB)-on-a-chip models that more closely resemble the structure and functions found in vivo.

Research motivation

iPSC-derived BBB models on-a-chip are a promising field that still lacks improvements and uniformity within the specialized literature.

Research objectives

To search the literature and analyze the selected data on the cultivation of iPSCs within microfluidic environments to mimic the human BBB.

Research methods

A literature search using the PRISMA approach using the following terms: “iPSC,” “BBB,” and “microfluidic device,” wherein 14 studies were selected based on the inclusion and exclusion criteria, and data were organized into three tables and one flow chart.

Research results

Studies have been found from 2017 to 2022, wherein the microdevices were either commercially available or manufactured in-house using soft-lithography. iPSCs were differentiated into endothelial or neural cells and seeded in the chips individually or in co-culture onto an extracellular-matrix layer mainly made of collagen IV/fibronectin. The selected studies focused principally on the structural and functional design of the human BBB model on-a-chip, displaying future application potential for drug screening and disease modeling.

Research conclusions

Despite the lack of consensus in protocols, the studies analyzed herein were able to efficiently reproduce a human microfluidic BBB in vitro making use of iPSCs.

Research perspectives

The developed BBB models on-a-chip have shown great potential to study physiopathological conditions related to the central nervous system, to apply advanced technology approaches for novel therapies (drug delivery through nanoparticles), and to develop genetic modification therapies for BBB dysfunctions through clustered regularly interspaced short palindromic repeats methodologies.