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

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 more limited differentiation capacity than embryonic stem cells, they are easily obtained from 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.


To evaluate the cell differentiation capacity of human breastmilk stem cells for the three germ layers by a systematic review.


The searched databases were PubMed, EMBASE, OVID, and COCHRANE LIBRARY, published between 2007 and 2018 in the English language. All were in vitro studies for analysis of the "cell differentiation potential" in the literature using the keywords “human breastmilk,” “stem cells,” and keywords combined with the Boolean operator “NOT” were used to exclude those articles that had the word “CANCER” and their respective synonyms, which were previously consulted according to medical subject heading terms. PRISMA 2009 guidelines were followed in this study.


A total of 315 titles and abstracts of articles were examined. From these, 21 were in common with more than one database, leaving 294 articles for analysis. Of that total, five 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, of which NANOG, a critical regulator for self-renewal and maintenance, was the most highly expressed. Those cells have the ability to differentiate in vitro into adipocytes, chondrocytes, osteocytes, oligodendrocytes, astrocytes, and neurons as well hepatocytes, β-pancreatic cells, and cardiomyocytes.


Although the literature has been scarce, the pluripotentiality of these cells represents great potential for tissue engineering and cellular therapy. Further studies for safe clinical translation are needed.

Keywords: Human breastmilk, Stem cells, Cell differentiation, Pluripotency, Stemness

Core tip: Human breastmilk stem cells present interesting features that make them an alternative source of stem cells, mainly because they do not require any invasive procedure to be obtained. The objective was to investigate the literature data on their ability to differentiate into other cell lines. It was possible to verify that these cells have a high capacity of differentiation, as they are able to generate cells of the endoderm, mesoderm, and ectoderm lineages. However, the number of publications on the subject is still scarce, demonstrating that this source needs more studies and has the potential to be explored in regenerative medicine.