Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2020; 12(5): 381-405
Published online May 26, 2020. doi: 10.4252/wjsc.v12.i5.381
Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review
Mariana Penteado Nucci, Igor Salerno Filgueiras, João Matias Ferreira, Fernando Anselmo de Oliveira, Leopoldo Penteado Nucci, Javier Bustamante Mamani, Gabriel Nery Albuquerque Rego, Lionel Fernel Gamarra
Mariana Penteado Nucci, LIM44, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05529-060, Brazil
Igor Salerno Filgueiras, João Matias Ferreira, Fernando Anselmo de Oliveira, Javier Bustamante Mamani, Gabriel Nery Albuquerque Rego, Lionel Fernel Gamarra, Hospital Israelita Albert Einstein, São Paulo 05529-060, Brazil
Leopoldo Penteado Nucci, Centro Universitário do Planalto Central, Brasília, DF, Brazil
Author contributions: Nucci MP, Filgueiras IS and Gamarra LF, conceptualized and designed the review; Ferreira JM, Oliveira FA, Mamani JB and Rego GNA contributed to search of literature, data extraction and critical revision; Nucci MP, Nucci LP, Mamani JB and Gamarra LF carried out the analysis, drafted the manuscript and critical revision; all authors reviewed and approved the final manuscript as submitted.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR), No. CNPq-400856/2016-6; and São Paulo State Research Support Foundation, No. FAPESP:2014/50983-3 and No. FAPESP:2016/21470-3.
Conflict-of-interest statement: The authors have declared that no competing interests exist.
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:
Corresponding author: Lionel Fernel Gamarra, MSc, PhD, Academic Research, Associate Research Scientist, Postdoc, Professor, Reader in Health Technology Assessment, Senior Researcher, Statistician, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627/701 - Morumbi, São Paulo 05529-060, Brazil.
Received: January 23, 2020
Peer-review started: January 23, 2020
First decision: April 1, 2020
Revised: April 2, 2020
Accepted: April 23, 2020
Article in press: April 23, 2020
Published online: May 26, 2020
Research background

Stroke survivors commonly suffer from disabilities requiring temporary or lifelong assistance, resulting in a substantial economic burden for poststroke care and stem cell (SC) therapeutics appear to be a promising alternative for intervention in stroke therapy. However, the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time.

Research motivation

The analysis of the homing and tracking SC processes is a pivotal strategy for utilizing preclinical results to increase translational knowledge to improve stroke care at the bedside.

Research objectives

In this systematic review, we aim to evaluate SC migration homing, tracking and therapeutic efficacy in the treatment of stroke using nanoparticles.

Research methods

A systematic literature search was performed to identify articles published prior to November 2019 that were indexed in PubMed and Scopus. The following inclusion criteria were used: (1) Studies that used in vivo models of stroke or ischemic brain lesions; (2) Studies of SCs labeled with some type of contrast agent for cell migration detection; and (3) Studies that involved in vivo cellular homing and tracking analysis.

Research results

A total of 82 articles were identified by indexing in Scopus and PubMed. After the inclusion criteria were applied, 35 studies were selected, and the articles were assessed for eligibility; ultimately, only 25 studies were included. Most of the selected studies used SCs from human and mouse bone marrow labeled with magnetic nanoparticles alone or combined with fluorophore dyes. These cells were administered in the stroke model (to treat middle cerebral artery occlusion in 74% of studies and for photothrombotic induction in 26% of studies). Fifty-three percent of studies used xenogeneic grafts for cell therapy, and the migration homing and tracking evaluation was performed by magnetic resonance imaging as well as other techniques, such as near-infrared fluorescence imaging (12%) or bioluminescence assays (12%).

Research conclusions

Our systematic review provides a comprehensive, up-to-date evaluation of the SC migration and efficacy of cellular therapy for brain injury. Cellular therapy demonstrated considerable efficacy with regard to the functional and structural evaluation, as well as the differentiation of the cells in the late stage of evaluation (after 7 d of cell implantation), using protein molecular and other tests.

Research perspectives

In summary, a long clinical follow-up is necessary in combination with the use of the homing imaging technique as the gold standard to address the gap between the clinical application and the preclinical cellular therapy outcome. Thus, the prescription of SCs labeled with SPION according to this review may help improve future clinical trials.