Anti-tumor effects of engineered mesenchymal stem cells in colon cancer model
Jianying Yang1, Kui Lv1, Junfeng Sun1
1Department of Emergency, Anhui No. 2 Provincial People's Hospital, Hefei, People's Republic of China.
Background:
Cell-based gene therapy is considered as a promising strategy for the treatment of human malignancy. In many different types of cancer, mesenchymal stem cells (MSCs) are observed as valuable and potential anti-cancer agents. However, the exact mechanisms of MSCs involved in tumor microenvironment are not well understood.
Aim:
Our aims are to elucidate the MSCs-mediated tumor microenvironment.
Materials And Methods:
In this study, colon cancer model was established by injecting the HT29 cells into the subcutaneous of right axilla of nude mice. We applied the human placenta-derived MSCs (hP-MSCs) armed with a double fusion gene containing the herpes simplex virus truncated thymidine kinase and firefly luciferase for treatment of colon cancer on days 10, 15, and 20 after HT29 cells injection. Molecular imaging methods were used for real-time imaging tumor progression and tracking transplanted hP-MSCs by bioluminescence imaging. Furthermore, proliferation and apoptosis-related proteins levels in colon cancer tissues were examined by immunofluorescence and Western blotting.
Results:
Our results demonstrated that the administration of engineered hP-MSCs significantly inhibited the tumors and this effect was enhanced by ganciclovir application. Further analysis demonstrated the anti-tumor effect of engineered hP-MSCs in vivo depended on inhibiting tumor proliferation and inducing tumor apoptosis.
Conclusion:
Collectively, this work showed that engineered hP-MSCs could inhibit colon cancer progression and metastasis by inducing tumor cell death and suppressing proliferation.
Insights
Engineered human placenta-derived mesenchymal stem cells (hP-MSCs) effectively inhibit colon cancer progression. This anti-tumor effect is achieved by suppressing tumor cell proliferation and inducing apoptosis, with enhanced efficacy when combined with ganciclovir.
Area of Science:
- Oncology
- Stem Cell Biology
- Gene Therapy
Background:
- Mesenchymal stem cells (MSCs) show promise as anti-cancer agents for human malignancy.
- The precise mechanisms by which MSCs influence the tumor microenvironment remain unclear.
- Understanding MSCs' role is crucial for developing effective cell-based cancer therapies.
Purpose of the Study:
- To investigate the mechanisms of mesenchymal stem cells (MSCs) in mediating the tumor microenvironment.
- To evaluate the efficacy of engineered human placenta-derived MSCs (hP-MSCs) in a colon cancer model.
Main Methods:
- A colon cancer model was established using HT29 cells in nude mice.
- Engineered hP-MSCs, carrying a dual gene construct (HSV-tk and luciferase), were administered to treat colon cancer.
- Bioluminescence imaging tracked tumor progression and hP-MSC distribution; immunofluorescence and Western blotting analyzed proliferation and apoptosis markers.
Main Results:
- Engineered hP-MSCs significantly inhibited tumor growth in vivo.
- The anti-tumor effect was potentiated by the administration of ganciclovir.
- The observed anti-tumor activity was attributed to the suppression of tumor cell proliferation and the induction of tumor apoptosis.
Conclusions:
- Engineered hP-MSCs demonstrate significant potential for inhibiting colon cancer progression and metastasis.
- The therapeutic mechanism involves the induction of tumor cell death and the suppression of tumor cell proliferation.
- This study provides insights into the anti-tumor functions of engineered MSCs within the tumor microenvironment.
