231. A Stem Cell Approach for Cancer Blood Test

Abstract

Mesenchymal stem cells (MSC) are adult multipotent stem cells that possess regenerative and immunomodulatory properties. They have been widely investigated as therapeutic agents for a variety of disease conditions, including tissue repair, inflammation, autoimmunity and organ transplantation. Importantly, systemically-infused MSC selectively home to primary and metastatic tumors, though the molecular mechanisms of tumor tropism of MSC remain incompletely understood. We have exploited the active and selective MSC homing to cancer microenvironments to develop a rapid and selective blood test for the presence of cancer. Here we present the concept of using transplanted MSC as the basis for a simple cancer blood test. View Large Image | Download PowerPoint SlideMSC engineered to express humanized Gaussia luciferase (hGluc) co-localize with and persist in cancerous tissue, secreting hGluc into circulation that can be assayed in a minimally invasive fashion as a reporter for cancer presence. In vitro, hGluc secreted by engineered MSC can be detected stably over a period of days in the presence of serum. In vivo imaging showed that MSC homed to breast cancer lung metastases and persisted longer in tumor-bearing mice than in tumor-free mice (P < 0.05). hGluc activity in blood of tumor-bearing mice was significantly higher than in their tumor-free counterparts (P < 0.05). Both in vitro and in vivo data show that MSC expressing hGluc can identify and report small tumors or metastases in a simple blood test format. Our novel and simple stem cell-based blood test can potentially be used to screen, detect and monitor cancer and metastasis at early-stages and during treatment.