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Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
Acute myeloid leukemia cells and MSC-derived exosomes inhibiting transformation in myelodysplastic syndrome
Xiaoli Liu1, Fanggang Ren2,3, Shuo Li1
1Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, People's Republic of China.
Aims:
To investigate the mechanism of exosomes' role in the transformation of MDS to AML.
Methods:
Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size, and exosome protein surface markers. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their impacts on MDS cell microenvironment, proliferation, differentiation, cell cycle, and apoptosis were analyzed by CCK-8 assay and flow cytometry. Furthermore, exosomes from MSC were extracted for further authentication.
Results:
The transmission electron microscopy, nanoparticle tracking analysis, Western blotting, and flow cytometry methods all verify that ultrafiltration is a reliable method to extract exosomes in the culture medium. Exosomes from AML cell lines inhibit the proliferation of MDS cell lines, block cell cycle progression, and promote apoptosis and cell differentiation. It also leads to increased secretion of tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in MDS cell lines. In addition, MSC-derived exosomes were found to inhibit the proliferation of MDS cell lines, arrest cell cycle progression, promote apoptosis, and inhibit differentiation.
Conclusion:
Ultrafiltration is a proper methodology in extracting exosomes. The exosomes of AML origin and MSC origin may play a role in MDS leukemia transformation via targeting TNF-α/ROS-Caspase3 pathway.
Insights
Exosomes from acute myeloid leukemia (AML) and mesenchymal stem cells (MSC) can influence myelodysplastic syndromes (MDS) transformation. These exosomes impact MDS cell proliferation, apoptosis, and differentiation, potentially via the TNF-α/ROS-Caspase3 pathway.
Area of Science:
- Cell Biology
- Cancer Research
- Hematology
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- MDS can transform into acute myeloid leukemia (AML), a more aggressive cancer.
- The role of exosomes in MDS to AML transformation is not fully understood.
Purpose of the Study:
- To investigate the mechanism of exosome-mediated transformation of MDS to AML.
- To analyze the impact of AML-derived and MSC-derived exosomes on MDS cells.
Main Methods:
- Exosomes were extracted from MDS and AML cell lines using ultrafiltration.
- Exosome identification was performed via morphology, size, and surface markers.
- Co-culture experiments with MDS cell lines and analysis using CCK-8 assay and flow cytometry were conducted.
Main Results:
- Ultrafiltration proved effective for exosome extraction.
- AML-derived exosomes inhibited MDS cell proliferation, induced apoptosis and differentiation, and increased TNF-α and ROS secretion.
- MSC-derived exosomes also inhibited MDS cell proliferation and apoptosis but suppressed differentiation.
Conclusions:
- Ultrafiltration is a suitable method for exosome isolation.
- Exosomes from AML and MSC origins may drive MDS to AML transformation.
- The TNF-α/ROS-Caspase3 pathway is implicated in this process.

