Systematic Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2019; 11(11): 1005-1019
Published online Nov 26, 2019. doi: 10.4252/wjsc.v11.i11.1005
In vitro differentiation capacity of human breastmilk stem cells: A systematic review
Camila Maria Ribeiro Pacheco, Priscila Elias Ferreira, Claudia Sayuri Saçaki, Luana Alves Tannous, Idiberto José Zotarelli-Filho, Luiz Cesar Guarita-Souza, Katherine Athayde Teixeira de Carvalho
Camila Maria Ribeiro Pacheco, Priscila Elias Ferreira, Claudia Sayuri Saçaki, Katherine Athayde Teixeira de Carvalho, Cell Therapy and Biotechnology in Regenerative Medicine Department, Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research and Pequeno Príncipe Faculty, Curitiba 80.240-020, Paraná, Brazil
Luana Alves Tannous, Luiz Cesar Guarita-Souza, PUCPR-Institute of Biological and Health Sciences, CCBS, Curitiba 80.215-901, Paraná, Brazil
Idiberto José Zotarelli-Filho, Post Graduate and Continuing Education (Unipos), Department of Scientific Production, São José do Rio Preto 15.020-040, São Paulo, Brazil
Author contributions: Pacheco CMR collected the data and drafted this manuscript; Ferreira PE collected the data and revised references; Saçaki CS collected the data; Tannous LA revised the draft; Zotarelli-Filho IJ revised the Prisma 2009; Guarita-Souza LC proposed some discussions in this work; de Carvalho KAT designed the systematic review and performed the data analysis; All authors read and approved the final manuscript.
Supported by Araucária Foundation (Paraná State-Brazil); and the Coordination for the Improvement of Higher Education Personnel-Brazil (Capes), Financial code 001
Conflict-of-interest statement: The authors have no potential conflicts of interests to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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:
Corresponding author: Katherine Athayde Teixeira de Carvalho, MD, MsC, PhD, Professor, Cell Therapy and Biotechnology in Regenerative Medicine Department, Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research and Pequeno Príncipe Faculty, Ave. Silva Jardim, n°1632, Curitiba 80.240-020, Paraná, Brazil.
Received: April 3, 2019
Peer-review started: April 4, 2019
First decision: June 6, 2019
Revised: July 17, 2019
Accepted: September 4, 2019
Article in press: September 4, 2019
Published online: November 26, 2019
Research background

Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin; although those cells have a more limited differentiation capacity than embryonic stem cells, they are easily obtained from the somatic tissue and can be grown in large quantities. This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases, such as neurodegenerative diseases.

Research motivation

Mammary epithelium has been the focus of studies due to its remarkable population of human breastmilk stem cells (hBSCs). It will be important to evaluate the scientific literature as to the potential for differentiation of these cells for regenerative medicine.

Research objectives

The main objective was to evaluate the cell differentiation capacity of hBSCs for the three germ layers through a systematic review.

Research methods

The searched databases were PubMed, EMBASE, OVID, and COCHRANE LIBRARY; the inclusion criteria were all papers that: (1) addressed the plasticity of stem cells derived from human breastmilk, that is, the ability of the cell to differentiate into more than one cell line; (2) published between 2007 and 2018 in the English language; and (3) were in vitro studies for the analysis of the "cell differentiation potential" in the literature using the keywords "HUMAN BREASTMILK," "STEM CELLS," and keywords combined with the Boolean operator "NOT" used to exclude those articles that had the word "CANCER" and their respective synonyms, which were previously consulted according to the medical subject heading terms. PRISMA 2009 guidelines were followed in this study.

Research results

A total of 315 titles and abstracts of articles were examined. From these, 21 were in common with more than one database; remaining 294 articles. Out of that total, 5 publications met the inclusion criteria. When analyzing the publications, it was demonstrated that human breastmilk stem cells have a high cellular plasticity, exhibiting the ability to generate cells of all three germ layers: endoderm, mesoderm and ectoderm, demonstrating their stemness. Those cells expressed the genes, TRA-1-60/81, octamer-binding transcription factor 4, and NANOG; NANOG was the gene most highly expressed, which is a regulator for self-renewing and its maintenance. Those cells have the ability to differentiate in vitro: adipocytes, chondrocytes, osteocytes, oligodendrocytes, astrocytes, neurons as well hepatocytes, β-pancreatic cells, and cardiomyocytes.

Research conclusions

The hBSCs expressed the genes, TRA-1-60/81, NANOG, and Oct4. The pluripotentiality of hBSCs has been demonstrated by its NANOG expression, which is a regulator for self-renewal and its maintenance. This study opens the possibilities to use this source of adult stem cells for tissue engineering and cellular therapy. hBSCs demonstrated their stemness by high cellular plasticity and exhibiting the ability to generate cells of all three germ layers.

Research perspectives

There will be great potential of hBSCs for tissue engineering and cellular therapy, but more studies for a safe translation will be needed. The single cell analysis seems to be the best method for the next step to evaluate the genetic stability of hBSCs.