Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2019; 11(6): 347-374
Published online Jun 26, 2019. doi: 10.4252/wjsc.v11.i6.347
Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues
Urszula Kozlowska, Agnieszka Krawczenko, Katarzyna Futoma, Tomasz Jurek, Marta Rorat, Dariusz Patrzalek, Aleksandra Klimczak
Urszula Kozlowska, Agnieszka Krawczenko, Katarzyna Futoma, Aleksandra Klimczak, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw 53-114, Poland
Tomasz Jurek, Marta Rorat, Department of Forensic Medicine, Wroclaw Medical University, Wroclaw 50-345, Poland
Dariusz Patrzalek, Faculty of Health Science, Department of Physiotherapy, Wroclaw Medical University, Wroclaw 50-367, Poland
Author contributions: Kozlowska U performed the majority of experiments, analyzed the data, and wrote the paper; Krawczenko A, and Futoma K contributed to experiment preparation and acquisition and interpretation of data; Jurek T, Rorat M, and Patrzalek D contributed to material and data acquisition; Klimczak A designed the study, analyzed data, and wrote the paper.
Supported by the National Science Center, No. N407121940; and by the Wroclaw Centre of Biotechnology, the Leading National Research Centre (KNOW) program for the years 2014-2018.
Institutional review board statement: Research was performed using human samples and was approved by the institutional review board of the Bioethics Committee of Wroclaw Medical University No. KB-746/2012 and No. KB 201/2016.
Institutional review board statement: The Institutional Animal Care and Use Committee Approval Form is not applicable for the manuscript. Studies were not performed on animal models.
Conflict-of-interest statement: The authors declare that there is no conflict of interests regarding the publication of this paper.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE Guidelines Checklist is not applicable for the manuscript, studies were not performed on animal models.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Aleksandra Klimczak, DSc, PhD, Associate Professor, Laboratory of Biology of Stem and Neoplastic Cells, Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Rudolfa Weigla 12 Street, Wroclaw 53-114, Poland. aleksandra.klimczak@hirszfeld.pl
Telephone: +48-71-3371172 Fax: +48-71-3372171
Received: October 27, 2018
Peer-review started: October 27, 2018
First decision: November 15, 2018
Revised: December 3, 2018
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: June 26, 2019
Processing time: 242 Days and 17.1 Hours
Abstract
BACKGROUND

Mesenchymal stromal/stem cells (MSCs) constitute a promising tool in regenerative medicine and can be isolated from different human tissues. However, their biological properties are still not fully characterized. Whereas MSCs from different tissue exhibit many common characteristics, their biological activity and some markers are different and depend on their tissue of origin. Understanding the factors that underlie MSC biology should constitute important points for consideration for researchers interested in clinical MSC application.

AIM

To characterize the biological activity of MSCs during longterm culture isolated from: bone marrow (BM-MSCs), adipose tissue (AT-MSCs), skeletal muscles (SM-MSCs), and skin (SK-MSCs).

METHODS

MSCs were isolated from the tissues, cultured for 10 passages, and assessed for: phenotype with immunofluorescence and flow cytometry, multipotency with differentiation capacity for osteo-, chondro-, and adipogenesis, stemness markers with qPCR for mRNA for Sox2 and Oct4, and genetic stability for p53 and c-Myc; 27 bioactive factors were screened using the multiplex ELISA array, and spontaneous fusion involving a co-culture of SM-MSCs with BM-MSCs or AT-MSCs stained with PKH26 (red) or PKH67 (green) was performed.

RESULTS

All MSCs showed the basic MSC phenotype; however, their expression decreased during the follow-up period, as confirmed by fluorescence intensity. The examined MSCs express CD146 marker associated with proangiogenic properties; however their expression decreased in AT-MSCs and SM-MSCs, but was maintained in BM-MSCs. In contrast, in SK-MSCs CD146 expression increased in late passages. All MSCs, except BM-MSCs, expressed PW1, a marker associated with differentiation capacity and apoptosis. BM-MSCs and AT-MSCs expressed stemness markers Sox2 and Oct4 in long-term culture. All MSCs showed a stable p53 and c-Myc expression. BM-MSCs and AT-MSCs maintained their differentiation capacity during the follow-up period. In contrast, SK-MSCs and SM-MSCs had a limited ability to differentiate into adipocytes. BM-MSCs and AT-MSCs revealed similarities in phenotype maintenance, capacity for multilineage differentiation, and secretion of bioactive factors. Because AT-MSCs fused with SM-MSCs as effectively as BM-MSCs, AT-MSCs may constitute an alternative source for BM-MSCs.

CONCLUSION

Long-term culture affects the biological activity of MSCs obtained from various tissues. The source of MSCs and number of passages are important considerations in regenerative medicine.

Keywords: Mesenchymal stem/progenitor cells; Bone marrow MSCs; Adipose tissue MSCs; Muscle-derived MSCs; Skin-derived MSCs; Cytokines and trophic factors of MSCs; Spontaneous fusion of MSCs

Core tip: A comprehensive characterization of mesenchymal stromal/stem cells (MSCs) with different tissue origin during long-term culture was demonstrated in terms of: basic phenotype strength, stemness and genetic stability, and ability to secrete bioactive factors and affect one another in co-culture. MSCs were phenotypically heterogeneous and showed diverse differentiation potentials and secretion of bioactive factors associated with tissue origin. Bone marrow (BM)-MSCs and adipose tissue (AT)-MSCs expressed stemness markers Sox2 and Oct4 in long-term culture, whereas skeletal muscles (SM)-MSCs and skin (SK)-MSCs did not. All MSCs were stable for p53 and c-Myc expression. AT-MSCs fused with SM-MSCs as effectively as BM-MSCs. Long-term culture affected the biological properties of the MSCs.