Basic Study
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World J Stem Cells. Apr 26, 2024; 16(4): 434-443
Published online Apr 26, 2024. doi: 10.4252/wjsc.v16.i4.434
Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages
Fatimah Almahasneh, Ejlal Abu-El-Rub, Ramada R Khasawneh, Rawan Almazari
Fatimah Almahasneh, Ejlal Abu-El-Rub, Ramada R Khasawneh, Rawan Almazari, Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan
Author contributions: Abu-El-Rub E conceptualized the study; Almahasneh F, Abu-El-Rub E, Khasawneh RR, and Almazari R carried out the experiments; Almahasneh F and Abu-El-Rub E analyzed the data, revised and formatted the content of the manuscript and verified spelling, punctuation and grammatical errors; Almahasneh F drafted and wrote the manuscript; and all authors have read and approve the final manuscript.
Supported by the Deanship of Scientific Research, Yarmouk University, Jordan, No. 73/2022.
Institutional review board statement: Institutional review board approval was not needed for this study because the human cell lines used for this study were commercially purchased.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: Ejlal Abu-El-Rub, PharmD, PhD, Assistant Professor, Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid-Shafiq Irshidat Street, Irbid 21163, Jordan. ejlal.abuelrub@yu.edu.jo
Received: December 30, 2023
Peer-review started: December 30, 2023
First decision: January 23, 2024
Revised: February 5, 2024
Accepted: March 18, 2024
Article in press: March 18, 2024
Published online: April 26, 2024
Processing time: 116 Days and 8 Hours
Abstract
BACKGROUND

Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic potential, due to their regenerative and immunomodulatory properties. Serial passage and stress factors may affect the biological characteristics of MSCs, but the details of these effects have not been recognized yet.

AIM

To investigate the effects of stress factors (high glucose and severe hypoxia) on the biological characteristics of MSCs at different passages, in order to optimize the therapeutic applications of MSCs.

METHODS

In this study, we investigated the impact of two stress conditions; severe hypoxia and high glucose on human adipose-tissue derived MSCs (hAD-MSCs) at passages 6 (P6), P8, and P10. Proliferation, senescence and apoptosis were evaluated measuring WST-1, senescence-associated beta-galactosidase, and annexin V, respectively.

RESULTS

Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control, while the extent of senescence did not change significantly under stress conditions. At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6. Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage, while no change in apoptosis was observed. On the other hand, MSCs cultured under hypoxia showed decreased senescence, increased apoptosis and no significant change in proliferation when compared to the same conditions at P8.

CONCLUSION

These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages, and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.

Keywords: Mesenchymal stem cells; High glucose; Hypoxia; Stressful microenvironment; Serial passage; Senescence; Apoptosis

Core Tip: Mesenchymal stem cells (MSCs) are increasingly being used for the treatment of various diseases due to their immunomodulatory and regenerative properties, but serial passages needed for MSCs expansion and stress factors found in the diseased tissues may compromise their therapeutic potential. Investigating the effects of stress factors (high glucose and severe hypoxia) on the biological characteristics of MSCs at different passages will help optimize the clinical uses of MSCs and their expected outcomes.