Multipotent Stromal Cells in a Tumor Microenvironment

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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Phenotype molding of stromal cells in the lung tumor microenvironment

Nature Medicine ◽

10.1038/s41591-018-0096-5 ◽

2018 ◽

Vol 24 (8) ◽

pp. 1277-1289 ◽

Cited By ~ 308

Author(s):

Diether Lambrechts ◽

Els Wauters ◽

Bram Boeckx ◽

Sara Aibar ◽

David Nittner ◽

...

Keyword(s):

Tumor Microenvironment ◽

Stromal Cells ◽

Lung Tumor

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Role of CD8+ T lymphocyte cells: Interplay with stromal cells in tumor microenvironment

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2021.03.027 ◽

2021 ◽

Author(s):

Qin Xie ◽

Jian Ding ◽

Yi Chen

Keyword(s):

Tumor Microenvironment ◽

T Lymphocyte ◽

Stromal Cells ◽

Cd8 T Lymphocyte

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Some Special Aspects of Liver Repair after Resection and Administration of Multipotent Stromal Cells in Experiment

Life ◽

10.3390/life11010066 ◽

2021 ◽

Vol 11 (1) ◽

pp. 66

Author(s):

Igor Maiborodin ◽

Elena Lushnikova ◽

Marina Klinnikova ◽

Swetlana Klochkova

Keyword(s):

Bone Marrow ◽

Liver Resection ◽

Connective Tissue ◽

Light Microscopy ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Multipotent Stromal Cells ◽

Rapid Restoration ◽

Bone Marrow Origin

Changes in rat liver after resection and injection of autologous multipotent mesenchymal stromal cells of bone marrow origin (MSCs) transfected with the GFP gene and cell membranes stained with red-fluorescent lipophilic membrane dye were studied by light microscopy. It was found that after the introduction of MSCs into the damaged liver, their differentiation into any cells was not found. However, under the conditions of MSCs use, the number of neutrophils in the parenchyma normalizes earlier, and necrosis and hemorrhages disappear more quickly. It was concluded that the use of MSCs at liver resection for the rapid restoration of an organ is inappropriate, since the injected cells in vivo do not differentiate either into hepatocytes, into epithelial cells of bile capillaries, into endotheliocytes and pericytes of the vascular membranes, into fibroblasts of the scar or other connective tissue structures, or into any other cells present in the liver.

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Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells

Cancers ◽

10.3390/cancers13133191 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3191

Author(s):

Katherine Po Sin Chung ◽

Rainbow Wing Hei Leung ◽

Terence Kin Wah Lee

Keyword(s):

Stem Cells ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Stromal Cells ◽

Current Knowledge ◽

Special Focus ◽

Intrinsic Regulation ◽

Mechanistic Basis ◽

Novel Therapeutic Strategies

Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.

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The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment

Technology in Cancer Research & Treatment ◽

10.1177/1533033820920969 ◽

2020 ◽

Vol 19 ◽

pp. 153303382092096

Author(s):

Hongzhi Sun ◽

Bo Zhang ◽

Haijun Li

Keyword(s):

Tumor Microenvironment ◽

Pancreatic Ductal Adenocarcinoma ◽

Stromal Cells ◽

Genomic Analysis ◽

Ductal Adenocarcinoma ◽

Genetic Mutations ◽

Cellular Processes ◽

Dismal Prognosis ◽

Mutant Genes

Pancreatic ductal adenocarcinoma has extremely high malignancy and patients with pancreatic ductal adenocarcinoma have dismal prognosis. The failure of pancreatic ductal adenocarcinoma treatment is largely due to the tumor microenvironment, which is featured by ample stromal cells and complicated extracellular matrix. Recent genomic analysis revealed that pancreatic ductal adenocarcinoma harbors frequently mutated genes including KRAS, TP53, CDKN2A, and SMAD4, which can widely alter cellular processes and behaviors. As shown by accumulating studies, these mutant genes may also change tumor microenvironment, which in turn affects pancreatic ductal adenocarcinoma progression. In this review, we summarize the role of such genetic mutations in tumor microenvironment regulation and potential mechanisms.

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