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Updated: Feb 27, 2026
Exploring the Potential of Mesenchymal Stem Cell Sheet on The Development of Hepatocellular Carcinoma In Vivo
Published on: September 11, 2018
Inhibitory Effect and Mechanism of Mesenchymal Stem Cells Cultured in 3D System on Hepatoma Cells HepG2
Diandian Zhao1, Lingling Hou2, Mengwu Pan1
1College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, People's Republic of China.
Abstract:
Mesenchymal stem cells (MSCs) exhibit the feature of homing to tumor site and being immunosuppressive, which have broad prospects in tumor therapy. However, MSCs are commonly cultured in a two-dimensional (2D) condition, which would gradually loss some in vivo important properties. In this study, we built a three-dimensional (3D) system with collagen/Matrigel scaffolds to culture MSCs. The results indicated that MSCs in 3D scaffolds showed higher proliferation ability than that of in 2D cells. In vitro, 3D-cultured MSC-conditioned media (CM) significantly inhibited the proliferation of hepatoma cells HepG2 than that of in 2D-cultured MSC-CM and control groups. In vivo, animal transplantation experiment showed that the treatment of 3D-cultured MSC-CM could further significantly delay the tumor initiation and decrease the tumor volume. The microarray, quantitative PCR, and ELISA assay found that MSCs cultured in the 3D system expressed and secreted more amounts of IL-24. RT-PCR and western blot results showed that IL-24 can activate JAK1-STAT3 pathway via IL22R1 and IL20R2, and further inhibit the proliferation of HepG2 cells. Taken together, these results demonstrated that MSCs cultured in the 3D system had an inhibitory effect on the proliferation of HepG2 cells, probably through secreting more IL-24, which activated JAK1-STAT3 signaling and finally inhibited the cell proliferation to delay tumor initiation. This study also provided a simpler and more reliable approach for MSCs to suppress tumor cells, and provided effective experimental data for clinical treatment of tumor and experimental basis.
Insights
Three-dimensional (3D) culture enhances mesenchymal stem cells (MSCs) to inhibit hepatoma cell proliferation. This 3D system boosts MSCs
Area of Science:
- Oncology
- Stem Cell Biology
- Biotechnology
Background:
- Mesenchymal stem cells (MSCs) show promise in tumor therapy due to their homing and immunosuppressive properties.
- Traditional 2D cell culture methods can lead to loss of critical in vivo properties in MSCs.
- Developing advanced culture systems is crucial for optimizing MSC therapeutic potential.
Purpose of the Study:
- To investigate the impact of a 3D culture system on MSC properties and their anti-cancer effects.
- To evaluate the efficacy of 3D-cultured MSC-conditioned media (CM) against hepatoma cells (HepG2).
- To elucidate the molecular mechanisms underlying the enhanced anti-tumor activity of 3D-cultured MSCs.
Main Methods:
- Culturing MSCs in a 3D collagen/Matrigel scaffold system versus a 2D system.
- Assessing MSC proliferation in 2D and 3D cultures.
- Evaluating the inhibitory effects of 2D- and 3D-MSC-CM on HepG2 cell proliferation in vitro.
- Conducting animal transplantation experiments to assess in vivo anti-tumor efficacy.
- Utilizing microarray, quantitative PCR, ELISA, RT-PCR, and western blot to analyze gene and protein expression, focusing on IL-24 and the JAK1-STAT3 pathway.
Main Results:
- MSCs cultured in 3D scaffolds exhibited higher proliferation rates compared to 2D cultures.
- 3D-MSC-CM significantly inhibited HepG2 cell proliferation more effectively than 2D-MSC-CM.
- In vivo studies showed that 3D-MSC-CM treatment delayed tumor initiation and reduced tumor volume.
- MSCs in the 3D system secreted significantly higher levels of IL-24.
- IL-24 was found to activate the JAK1-STAT3 pathway via IL22R1 and IL20R2, leading to the inhibition of HepG2 cell proliferation.
Conclusions:
- 3D culture enhances MSCs' ability to suppress hepatoma cell proliferation, likely via increased IL-24 secretion.
- The IL-24 mediated activation of the JAK1-STAT3 pathway is a key mechanism for the anti-proliferative effect on HepG2 cells.
- This study presents a more effective approach for utilizing MSCs in tumor suppression and provides a basis for clinical applications.
