Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2022; 14(8): 658-679
Published online Aug 26, 2022. doi: 10.4252/wjsc.v14.i8.658
How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models
Murilo Montenegro Garrigós, Fernando Anselmo de Oliveira, Mariana Penteado Nucci, Leopoldo Penteado Nucci, Arielly da Hora Alves, Olivia Furiama Metropolo Dias, Lionel Fernel Gamarra
Murilo Montenegro Garrigós, Fernando Anselmo de Oliveira, Mariana Penteado Nucci, Arielly da Hora Alves, Olivia Furiama Metropolo Dias, Lionel Fernel Gamarra, Hospital Israelita Albert Einstein, São Paulo 05652-900, São Paulo, Brazil
Murilo Montenegro Garrigós, Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, São Paulo, Brazil
Mariana Penteado Nucci, LIM44-Hospital das Clínicas, Faculdade Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
Leopoldo Penteado Nucci, Centro Universitário do Planalto Central, Área Especial para Industria nº 02 Setor Leste - Gama-DF, Brasília 72445-020, Distrito Federal, Brazil
Author contributions: Garrigós MM, de Oliveira FA and Gamarra LF, conceptualized and designed the review; de Oliveira FA, and Garrigós MM contributed to search of literature, data extraction and critical revision; Nucci MP, Nucci LP, Dias OFM, Alves AH 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 CNPq, No. 308901/2020, No. 400856/2016-6; FAPESP, No. 2019/21070-3, No. 2017/17868-4, No. 2016/21470-3; SisNANO 2.0/MCTIC, No. 442539/2019-3; the National Institute of Science and Technology Complex Fluids (INCT-FCx); and “Amigos da Oncologia e Hematologia Einstein” AMIGOH.
Conflict-of-interest statement: The authors have declared that no competing interests exist.
PRISMA 2009 Checklist statement: The authors have read the PRISMA guideline 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, Full Professor, Research Scientist, Hospital Israelita Albert Einstein, Av Albert Einstein 640, São Paulo 05652-900, São Paulo, Brazil. lionelgamarra7@gmail.com
Received: March 15, 2022
Peer-review started: March 15, 2022
First decision: April 19, 2022
Revised: April 27, 2022
Accepted: July 26, 2022
Article in press: July 26, 2022
Published online: August 26, 2022
Processing time: 163 Days and 16.9 Hours
Abstract
BACKGROUND

Bone marrow transplantation (BMT) can be applied to both hematopoietic and nonhematopoietic diseases; nonetheless, it still comes with a number of challenges and limitations that contribute to treatment failure. Bearing this in mind, a possible way to increase the success rate of BMT would be cotransplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) to improve the bone marrow niche and secrete molecules that enhance the hematopoietic engraftment.

AIM

To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models.

METHODS

We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment. We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English. In PubMed, we initially identified 555 articles and after selection, only 12 were chosen. In Scopus, 2010 were identified, and six were left after the screening and eligibility process.

RESULTS

Of the 2565 articles found in the databases, only 18 original studies met the eligibility criteria. HSC distribution by source showed similar ratios, with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1 × 107 cells by intravenous or intrabone routes. However, MSCs had a high prevalence of human donors with a variety of sources (umbilical cord blood, bone marrow, tonsil, adipose tissue or fetal lung), using a lower dose, mainly 106 cells and ranging 104 to 1.5 × 107 cells, utilizing the same routes. MSCs were characterized prior to administration in almost every experiment. The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy. The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism, followed by hematopoietic reconstitution and survival analysis. Besides the engraftment, homing and cellularity were also evaluated in some studies.

CONCLUSION

The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models, in the absence of toxicity.

Keywords: Mesenchymal stem cells; Hematopoietic stem cells; Bone marrow transplantation; Co-transplantation; Hematopoietic reconstitution; Engraftment

Core Tip: The systematic review provided a current view on the characteristics of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) cotransplantation to achieve successful engraftment and improve hematopoietic reconstitution. The studies demonstrated a diversity in experimental designs and MSC isolation and characterization protocols; however, the lack of standardization in MSC use makes translation to clinical practice more difficult.