Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy

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.

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

“…10,41,42 BLI revealed that the survival of transplanted ADSCs could be significantly enhanced by CS-IGF-1C hydrogel application. Besides monitoring cell survival, molecular imaging also has been used for real-time visualization of VEGFR2 expressions in vivo, which provides direct evidence for disclosure of the therapeutic mechanism of angiogenesis.…”

Molecular Imaging of Inducible VEGF Expression and Tumor Progression in a Breast Cancer Model

“…Bioluminescence imaging (BLI) of luciferase reporter genes, as a powerful research strategy, has been used to monitor tumor growth and regression [3, 8, 9]. More importantly than this, two or more luciferase reporters with biochemical distinction can provide an opportunity to monitor different biological processes, such as exploration of the correlation between key protein activity and relative physiological states, tumor volume in tumor development [10], or evaluation of therapeutic efficacy in the same animal simultaneously and successively [3, 11]. …”

Pre- and postmortem imaging of transplanted cells

“…101 The variety of currently available luciferase types with different substrate specificities opens a new possibility to observe two or more cell lines simultaneously. Leng et al 102 adapted this idea to show the therapeutic effect of transplanted MSC in a model of human breast cancer. In this study, MSCs engineered to express RLuc were injected in mice bearing Fluc-expressing tumors, and due to different enzyme substrates, it enabled simultaneous detection of both MSCs and tumor cells.…”

“…This example showed that dual luciferase imaging enables investigation of the interaction between cell populations. 102 The principle of BLI is based on the luciferase reaction that requires an enzyme (firefly luciferase), its substrate (d-luciferin or coelenterazine), ATP, and oxygen. This enzyme-catalyzed oxidation results in oxyluciferin, a product that, when decaying, emits photons.…”