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Review
. 2021 Feb 11:8:617466.
doi: 10.3389/fcell.2020.617466. eCollection 2020.

Senescent Mesenchymal Stem Cells in Myelodysplastic Syndrome: Functional Alterations, Molecular Mechanisms, and Therapeutic Strategies

Xiaofang Chen  1 , Ningyu Li  1   2 , Jianyu Weng  1   2 , Xin Du  1   2
Affiliations
Review

Senescent Mesenchymal Stem Cells in Myelodysplastic Syndrome: Functional Alterations, Molecular Mechanisms, and Therapeutic Strategies

Xiaofang Chen et al. Front Cell Dev Biol. .

Abstract

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. However, therapies that are currently used to target hematopoietic stem cells are not effective. These therapies are able to slow the evolution toward acute myeloid leukemia but cannot eradicate the disease. Mesenchymal stem cells (MSCs) have been identified as one of the main cellular components of the bone marrow microenvironment, which plays an indispensable role in normal hematopoiesis. When functional and regenerative capacities of aging MSCs are diminished, some enter replicative senescence, which promotes inflammation and disease progression. Recent studies that investigated the contribution of bone marrow microenvironment and MSCs to the initiation and progression of the disease have offered new insights into the MDS. This review presents the latest updates on the role of MSCs in the MDS and discusses potential targets for the treatment of MDS.

Keywords: bone marrow microenvironment; mesenchymal stem cells; myelodysplastic syndrome; senescence; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Current treatment of MDS, based on the IPSS and revised IPSS and WHO-based Prognostic Scoring System for risk stratification (WPSS). EPO, erythropoietin; G-CSF, granulocyte colony-stimulating factor; IST, immunosuppressive therapy; HCT, hematopoietic cell transplantation.
Figure 2
Figure 2
The mechanism and dysfunction of MSC senescence in MDS. (1) Cells that contributed to MSCs, such as SSCs, neural crest-derived cells, and nes-CreER+ stromal cells, were reduced or depleted in MDS. In contrast, leptin receptors, which are detrimental to the function of MSCs, increased over time. (2) The senescence of MDS-MSCs may be related to increases in cell telomerase length, chromosome methylation status, abnormal proliferation regulation signal pathway, cell cycle arrest, and other factors. (3) The senescent MDS-MSCs exhibited reduced differentiation potential and stem cell support capacity.
See this image and copyright information in PMC

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