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Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells

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Abstract

Stemness pertains to the intrinsic ability of mesenchymal stem cells (MSCs) to undergo self-renewal and differentiate into multiple lineages, while simultaneously impeding their differentiation and preserving crucial differentiating genes in a state of quiescence and equilibrium. Owing to their favorable attributes, including uncomplicated isolation protocols, ethical compliance, and ease of procurement, MSCs have become a focal point of inquiry in the domains of regenerative medicine and tissue engineering. As age increases or ex vivo cultivation is prolonged, the functionality of MSCs decreases and their stemness gradually diminishes, thereby limiting their potential therapeutic applications. Despite the existence of several uncertainties surrounding the comprehension of MSC stemness, considerable advancements have been achieved in the clarification of the potential mechanisms that lead to stemness loss, as well as the associated strategies for stemness maintenance. This comprehensive review provides a systematic overview of the factors influencing the preservation of MSC stemness, the molecular mechanisms governing it, the strategies for its maintenance, and the therapeutic potential associated with stemness. Finally, we underscore the obstacles and prospective avenues in present investigations, providing innovative perspectives and opportunities for the preservation and therapeutic utilization of MSC stemness.

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Data Availability

All data (or sources thereof) relevant to this study are included in the article; further inquiries can be directed to the corresponding author/s.

Abbreviations

MSCs:

Mesenchymal stem cells

BMSCs:

Mesenchymal stem cells derived from bone marrow

ADSCs:

Adipose-derived mesenchymal stem cells

D-ASCs:

Mesenchymal stem cells derived from diabetic patients

UCMSCs:

Mesenchymal stem cells derived from the umbilical cord

WJ-MSCs:

Wharton's jelly mesenchymal stem cells

ABMSCs:

Alveolar bone-derived mesenchymal stromal cells

ROS:

Reactive oxygen species

NHE1:

The sodium/hydrogen exchanger 1

ESCs:

Embryonic stem cells

EPCAM:

Epithelial cell adhesion molecule

EPMC:

Ethyl p-methoxycinnamate

NF-κB:

The nuclear factor κB

HuR:

Human antigen R

snoRNPs:

Nucleolar ribonucleoprotein particles

SNORA7A:

Small nucleolar RNA 7A

DDR:

The DNA damage response

ASA:

Ascorbic acid

DMOG:

Dimethyloxallyl glycine

CREB1:

cAMP response element-binding protein 1

DPSCs:

Dental pulp stem cells

TSA:

Trichostatin A

OGC:

Octanoyl glycol chitosan

NsPEF:

Nanosecond pulsed electric fields

ECM:

The extracellular matrix

dECM:

Decellularized extracellular matrix

MS1:

Mile Sven1

PFB-F-GLU:

Glucosamine-based supramolecular hydrogel

SCDS:

Single-cell-derived spheres

iPSC:

Induced pluripotent stem cell

FGF:

Fibroblast growth factor

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Acknowledgements

This article is published as open access thanks to the generous financial support of the Central Hospital of Dalian University of Technology Department.

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Authors and Affiliations

  1. Central Hospital of Dalian University of Technology Department of Spine Surgery, Dalian, China

    Nizhou Jiang, Jiayu Hao, Jian Jiang & Hong Wang

  2. The First Affiliated Hospital of Dalian Medical University, Dalian, China

    Nizhou Jiang & Xiliang Tian

  3. Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China

    Quanxiang Wang

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  1. Nizhou Jiang
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  2. Xiliang Tian
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  3. Quanxiang Wang
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  4. Jiayu Hao
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  5. Jian Jiang
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  6. Hong Wang
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Contributions

Conceptualization, N.J., H.W., and J.J.; investigation, N.J. and H.W.; visualization, N.J., H.W., and Q.W.; writing—original draft preparation, N.J.; writing—review and editing, N.J. and J.J.; supervision, H.W.; funding acquisition, H.W.; J.J. and N.J. completed literature collection and manuscript writing. Other authors provided some guidance. Notably, J.J. contributed significantly to the improvement of the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jian Jiang or Hong Wang.

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Jiang, N., Tian, X., Wang, Q. et al. Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells. Stem Cell Rev and Rep 20, 455–483 (2024). https://doi.org/10.1007/s12015-023-10658-3

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