Abstract
IntroductionMesenchymal stem cells (MSCs) 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 MSCs selectively home to primary and metastatic tumors, though the molecular mechanisms of tumor tropism of MSCs remain incompletely understood. We have exploited the active and selective MSCs homing to cancer microenvironments to develop a rapid and selective blood test for the presence of cancer.MethodsWe tested the concept of using transplanted MSCs as the basis for a simple cancer blood test. MSCs were engineered to express humanized Gaussia luciferase (hGluc). In a minimally invasive fashion, hGluc secreted by MSCs into circulation as a reporter for cancer presence, was assayed to probe whether MSCs co-localize with and persist in cancerous tissue.ResultsIn vitro, hGluc secreted by engineered MSCs was detected stably over a period of days in the presence of serum. In vivo imaging showed that MSCs 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).ConclusionsBoth in vitro and in vivo data show that MSCs 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0151-9) contains supplementary material, which is available to authorized users.
Highlights
Mesenchymal stem cells (MSCs) are adult multipotent stem cells that possess regenerative and immunomodulatory properties
Both in vitro and in vivo data show that MSCs expressing humanized Gaussia luciferase (hGluc) can identify and report small tumors or metastases in a simple blood test format
Humanized Gaussia luciferase is secreted from engineered MSCs in vitro and is stable and detectable in blood Human bone marrow MSCs were stably transduced with lentivirus to express secreted humanized Gaussia luciferase as described above
Summary
Mesenchymal stem cells (MSCs) are adult multipotent stem cells that possess regenerative and immunomodulatory properties. In 2008, he received his Ph.D. in chemistry at McMaster University, where he focused on the use of functional nucleic acid to structure gold nanoparticles to construct well-defined nanostructures and biosensors He completed a Human Frontier Science Program Postdoctoral Fellow at Harvard Medical School, Brigham and Women’s Hospital and MIT, where he learned stem cell trafficking, and cell engineering for diagnostics and therapeutics. His current research focuses on the development of novel molecular, nano-, and micro-engineered tools for stem cell therapy and regenerative medicine, diagnosis and in vivo imaging, and elucidating stem cell and cancer biology
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