Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2019; 11(2): 100-123
Published online Feb 26, 2019. doi: 10.4252/wjsc.v11.i2.100
Triple-modal imaging of stem-cells labeled with multimodal nanoparticles, applied in a stroke model
Helio Rodrigues da Silva, Javier Bustamante Mamani, Mariana Penteado Nucci, Leopoldo Penteado Nucci, Andrea Tiemi Kondo, Daianne Maciely Carvalho Fantacini, Lucas Eduardo Botelho de Souza, Virginia Picanço-Castro, Dimas Tadeu Covas, José Mauro Kutner, Fernando Anselmo de Oliveira, Nelson Hamerschlak, Lionel Fernel Gamarra
Helio Rodrigues da Silva, Javier Bustamante Mamani, Andrea Tiemi Kondo, José Mauro Kutner, Fernando Anselmo de Oliveira, Nelson Hamerschlak, Lionel Fernel Gamarra, Hospital Israelita Albert Einstein, São Paulo 05651-900, Brazil
Mariana Penteado Nucci, LIM44, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, Brazil
Leopoldo Penteado Nucci, Centro Universitário do Planalto Central, Brasilia 72445-020, Brazil
Daianne Maciely Carvalho Fantacini, Lucas Eduardo Botelho de Souza, Virginia Picanço-Castro, Dimas Tadeu Covas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo 05403-010, Brazil
Author contributions: da Silva HR and Gamarra LF conceptualized the original idea; da Silva HR, Mamani JB, Nucci MP and Gamarra LF designed and performed the experiments and analyzed the data; Nucci LP and de Oliveira FA performed analysis of the data and animal management; Fantacini DMC, de Souza LEB, Picanço-Castro V and Covas DT performed the cellular culture for transduction of luciferase and the writing of the original draft; Kondo AT, Kutner JM, Nucci LP and Hamerschlak N performed the stem cell isolation and immunophenotype characterization; Mamani JB, Nucci MP, Nucci LP and Gamarra LF did the writing - original draft and writing - review and editing; Gamarra LF performed funding acquisition, investigation, project administration, resources and supervision.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, No. CNPq-465259/2014-6, and No. CNPq-400856/2016-6; São Paulo State Research Support Foundation, No. 2014/50983-3, and No. 2016/21470-3.
Institutional review board statement: The study was approved by the Ethics Committee for Research at the Instituto Israelita de Ensino e Pesquisa Albert Eisntein, Brazil (CAAE - 27665714.4.0000.0071) for the use of human mesenchymal stem cells after the donors informed consent.
Institutional animal care and use committee statement: The study was approved by the Ethics in Animal Research Committee of the Hospital Israelita Albert Einstein (HIAE) with approval number 1906-13. The vivarium of the Experimental Surgical Training Center (Centro de Experimentação e Treinamento em Cirurgia - CETEC) was accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC International).
Conflict-of-interest statement: The authors have declared that no competing interests exist.
Data sharing statement: The datasets supporting the conclusions of this article are included within in the article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines - Animal Research: Reporting In vivo Experiments, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lionel Fernel Gamarra, PhD, Senior Scientist, Group of nanobiotechnology of The Albert Einstein Hospital, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627/701 - Morumbi, São Paulo 05651-900, Brazil. lgamarra@einstein.br
Telephone: +55-11-21510243
Received: October 22, 2018
Peer-review started: October 23, 2018
First decision: November 14, 2018
Revised: December 5, 2018
Accepted: December 17, 2018
Article in press: December 17, 2018
Published online: February 26, 2019
Processing time: 128 Days and 8.9 Hours
Core Tip

Core tip: Multimodal imaging techniques provide morpho-functional information for studying pathological events following ischemia associated with new tracers. Molecular imaging innovations will contribute to the further understanding of stem cell transplantation, allowing an assessment of their therapeutic effects at the molecular scale. In this study, we evaluate the sensitivity of triple-modal imaging of human bone marrow mesenchymal stem cells labeled with multimodal nanoparticles (MNPs) to quantify the internalized iron load and cellular viability as well as the correlation of quantification results between the techniques. We demonstrate the importance of quantifying the MNP load internalized into cells via triple-image evaluation and the efficacy of signal detection in a stroke model.