Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy
Liang Leng1, Yuebing Wang2, Ningning He2
1Nankai University School of Medicine, Tianjin, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Science, Tianjin, China.
Abstract:
The tumor tropism of mesenchymal stem cells (MSCs) makes them an excellent delivery vehicle used in anticancer therapy. However, the exact mechanisms of MSCs involved in tumor microenvironment are still not well defined. Molecular imaging technologies with the versatility in monitoring the therapeutic effects, as well as basic molecular and cellular processes in real time, offer tangible options to better guide MSCs mediated cancer therapy. In this study, an in situ breast cancer model was developed with MDA-MB-231 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP). In mice breast cancer model, we injected human umbilical cord-derived MSCs (hUC-MSCs) armed with a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk), renilla luciferase (Rluc) and red fluorescent protein (RFP) into tumor on day 13, 18, 23 after MDA-MB-231 cells injection. Bioluminescence imaging of Fluc and Rluc provided the real time monitor of tumor cells and hUC-MSCs simultaneously. We found that tumors were significantly inhibited by hUC-MSCs administration, and this effect was enhanced by ganciclovir (GCV) application. To further demonstrate the effect of hUC-MSCs on tumor cells in vivo, we employed the near infrared (NIR) imaging and the results showed that hUC-MSCs could inhibit tumor angiogenesis and increased apoptosis to a certain degree. In conclusion, hUC-MSCs can inhibit breast cancer progression by inducing tumor cell death and suppressing angiogenesis. Moreover, molecular imaging is an invaluable tool in tracking cell delivery and tumor response to hUC-MSCs therapies as well as cellular and molecular processes in tumor.
Insights
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) showed significant breast cancer inhibition. Molecular imaging confirmed hUC-MSCs suppressed tumor growth, angiogenesis, and increased apoptosis, especially when combined with ganciclovir (GCV).
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Regenerative Medicine
Background:
- Mesenchymal stem cells (MSCs) exhibit tumor tropism, making them promising for cancer therapy.
- The precise mechanisms of MSCs within the tumor microenvironment require further elucidation.
- Molecular imaging offers real-time monitoring of therapeutic effects and cellular processes.
Purpose of the Study:
- To investigate the efficacy of human umbilical cord-derived MSCs (hUC-MSCs) in inhibiting breast cancer progression.
- To utilize molecular imaging for real-time tracking of hUC-MSCs and tumor response.
- To explore the combined therapeutic effect of hUC-MSCs and ganciclovir (GCV).
Main Methods:
- Development of an in situ breast cancer model using MDA-MB-231 cells with a dual reporter system (Fluc/eGFP).
- Intratumoral injection of hUC-MSCs engineered with a triple fusion gene (HSV-ttk/Rluc/RFP) into a mouse model.
- Simultaneous monitoring of tumor cells and hUC-MSCs using bioluminescence imaging (Fluc and Rluc) and near-infrared (NIR) imaging.
Main Results:
- hUC-MSCs administration significantly inhibited tumor growth in the breast cancer model.
- The combination of hUC-MSCs and ganciclovir (GCV) demonstrated enhanced tumor inhibition.
- Molecular imaging revealed that hUC-MSCs suppressed tumor angiogenesis and increased apoptosis.
Conclusions:
- hUC-MSCs effectively inhibit breast cancer progression through induction of tumor cell death and suppression of angiogenesis.
- Molecular imaging is a crucial tool for tracking cell delivery, monitoring tumor response, and understanding cellular processes in MSC-mediated cancer therapy.
- The combination of hUC-MSCs and GCV presents a potentially synergistic approach for breast cancer treatment.
