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

Stroke is the second leading cause of death worldwide. There is a real need to develop treatment strategies for reducing neurological deficits in stroke survivors, and stem cell (SC) therapeutics appear to be a promising alternative for stroke therapy that can be used in combination with approved thrombolytic or thrombectomy approaches. However, the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time. Nonetheless, tracking SCs from their niche to the target tissues is a complex process.


To evaluate SC migration homing, tracking and therapeutic efficacy in the treatment of stroke using nanoparticles


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.


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%).


Our systematic review provided an up-to-date evaluation of SC migration homing and the efficacy of cellular therapy for stroke treatment in terms of functional and structural improvements in the late stage.

Keywords: Stem cell, Nanoparticles, Homing, Tracking, Near-infrared fluorescence image, Cellular therapy, Magnetic resonance image, Bioluminescence, Stroke

Core tip: The systematic review provided an up-to-date evaluation of stem cell (SC) migration homing, using nanoparticles based on the technical and scientific aspects and combined molecular images. Thus, the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time, providing functional and structural outcomes in preclinical studies, but limited evidence of outcomes in clinical studies.