title: Exogenous marker-engineered mesenchymal stem cells detect cancer and metastases in a simple blood assay.
abstract: BACKGROUND
  Mesenchymal 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  Both 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. linanl@uci.edu.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. linanl@uci.edu.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. linanl@uci.edu.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. linanl@uci.edu.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. linanl@uci.edu.
authors.forename: Linan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. shirlexz@uci.edu.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. shirlexz@uci.edu.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. shirlexz@uci.edu.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. shirlexz@uci.edu.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. shirlexz@uci.edu.
authors.forename: Shirley X
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. r.aeran@gmail.com.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. r.aeran@gmail.com.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. r.aeran@gmail.com.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. r.aeran@gmail.com.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. r.aeran@gmail.com.
authors.forename: Rangoli
authors.initials: R
authors.lastname: Aeran
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. wenbinl1@uci.edu.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. wenbinl1@uci.edu.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. wenbinl1@uci.edu.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. wenbinl1@uci.edu.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. wenbinl1@uci.edu.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. mengrol@uci.edu.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. mengrol@uci.edu.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. mengrol@uci.edu.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. mengrol@uci.edu.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. mengrol@uci.edu.
authors.forename: Mengrou
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. geopolovin@gmail.com.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. geopolovin@gmail.com.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. geopolovin@gmail.com.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. geopolovin@gmail.com.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. geopolovin@gmail.com.|Department of Biological Sciences, California State University, Long Beach, 1250 Bellflower Boulevard, Long Beach, CA, 90840, USA. geopolovin@gmail.com.
authors.forename: George
authors.initials: G
authors.lastname: Polovin
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. epone@uci.edu.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. epone@uci.edu.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. epone@uci.edu.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. epone@uci.edu.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. epone@uci.edu.
authors.forename: Egest J
authors.initials: EJ
authors.lastname: Pone
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. weianz@uci.edu.|Department of Biomedical Engineering, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. weianz@uci.edu.|Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. weianz@uci.edu.|Chao Family Comprehensive Cancer Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. weianz@uci.edu.|Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. weianz@uci.edu.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060846:Cell Engineering; D005260:Female; D064593:Heterografts; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D059630:Mesenchymal Stem Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation
chemical_list: D008156:Luciferases