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Potential functions and therapeutic implications of glioma-resident mesenchymal stem cells

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Abstract

Mesenchymal stem cells (MSCs) are emerging crucial regulators in the tumor microenvironment (TME), which contributes to tumor progression and therapeutic resistance. MSCs are considered to be the stromal components of several tumors, their ultimate contribution to tumorigenesis and their potential to drive tumor stem cells, especially in the unique microenvironment of gliomas. Glioma-resident MSCs (GR-MSCs) are non-tumorigenic stromal cells. The phenotype of GR-MSCs is similar to that of prototype bone marrow-MSCs and GR-MSCs enhance the GSCs tumorigenicity via the IL-6/gp130/STAT3 pathway. The higher percentage of GR-MSCs in TME results in the poor prognosis of glioma patients and illuminate the tumor-promoting roles for GR-MSCs by secreting specific miRNA. Furthermore, the GR-MSC subpopulations associated with CD90 expression determine their different functions in glioma progression and CD90low MSCs generate therapeutic resistance by increasing IL-6-mediated FOXS1 expression. Therefore, it is urgent to develop novel therapeutic strategies targeting GR-MSCs for GBM patients. Despite that several functions of GR-MSCs have been confirmed, their immunologic landscapes and deeper mechanisms associated with the functions are not still expounded. In this review, we summarize the progress and potential function of GR-MSCs, as well as highlight their therapeutic implications based on GR-MSCs in GBM patients.

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Abbreviations

MSCs:

Mesenchymal stem cells

GR-MSCs:

Gioma-resident mesenchymal stem cells

GA-MSCs:

Gioma-associated mesenchymal stem cells

TA-MSCs:

Tumor-associated mesenchymal stem cells

TME:

Tumor microenvironment

GBM:

Glioblastoma

GSCs:

Glioma stem cells

IDO:

Indoleamine 2,3-dioxygenase

PGE2:

Prostaglandin E2

Tregs:

Regulatory B cells

PD-1:

Programmed death protein 1

PD-L1:

Programmed death ligand 1

NK:

Natural killer

DCs:

Dendritic cells

EMT:

Epithelial-mesenchymal transition

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Acknowledgements

Fig. 1, Fig. 2, Fig. 4 and graphical abstract used in this article were created using BioRender.com. Fig. 3 was created using ScienceSlides.

Funding

This work was supported by grants from the Beijing Natural Science Foundation Program and Scientific Research Key Program of the Beijing Municipal Commission of Education (KZ202010025034), the Capital’s Funds for Health Improvement and Research (CFH, 2020-1-1071), the National Natural Science Foundation of China (No, 81972344) and the Beijing Laboratory of Biomedical Materials Foundation.

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Author notes

  1. Qing Zhang and Jialin Wang contributed equally to this manuscript.

Authors and Affiliations

  1. Brain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Qing Zhang, Jialin Wang, Junwen Zhang & Fusheng Liu

  2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Qing Zhang, Jialin Wang & Fusheng Liu

  3. Beijing Laboratory of Biomedical Materials, Beijing, China

    Qing Zhang, Jialin Wang, Junwen Zhang & Fusheng Liu

  4. Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Qing Zhang

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  1. Qing Zhang
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  2. Jialin Wang
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  4. Fusheng Liu
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Contributions

Q.Z. wrote the manuscript text and prepared Figs. 1, 2, 4 and Table 1. J.L.W. wrote the manuscript text and prepared Fig 3. J.W.Z. collected the partial literature. F.S.L. provided the funding and revised the manuscript. All authors approved the version.

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Correspondence to Fusheng Liu.

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Zhang, Q., Wang, J., Zhang, J. et al. Potential functions and therapeutic implications of glioma-resident mesenchymal stem cells. Cell Biol Toxicol 39, 853–866 (2023). https://doi.org/10.1007/s10565-023-09808-7

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