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Rapid Communication| Volume 19, ISSUE 12, P1537-1545, December 2017

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An engineered biomarker system to monitor and modulate immune clearance of cell therapies

  • Amy Singleton
    Affiliations
    Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Shriners Hospitals for Children, Boston, Massachusetts, USA
    Search for articles by this author
  • Danika Khong
    Affiliations
    Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Shriners Hospitals for Children, Boston, Massachusetts, USA
    Search for articles by this author
  • Ling-Yee Chin
    Affiliations
    Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Shriners Hospitals for Children, Boston, Massachusetts, USA
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  • Shilpaa Mukundan
    Affiliations
    Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Shriners Hospitals for Children, Boston, Massachusetts, USA
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  • Matthew Li
    Affiliations
    Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Shriners Hospitals for Children, Boston, Massachusetts, USA
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  • Biju Parekkadan
    Correspondence
    Correspondence: Biju Parekkadan, PhD, Shriners Hospitals for Children, 51 Blossom Street, Boston, Massachusetts 02114, USA.
    Affiliations
    Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Shriners Hospitals for Children, Boston, Massachusetts, USA

    Harvard Stem Cell Institute, Cambridge, Massachusetts, USA

    Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA
    Search for articles by this author
Published:September 13, 2017DOI:https://doi.org/10.1016/j.jcyt.2017.08.003

      Abstract

      Background aims

      Cell transplants offer a new opportunity to deliver therapies with novel and complex mechanisms of action. Understanding the pharmacology of cell transplants is important to deliver this new therapy effectively. Currently, however, there are limited techniques to easily track cells after intravenous administration due to the dispersion of the graft throughout the entire body.

      Methods

      We herein developed an engineered cell system that secretes a luciferase enzyme to sensitively detect cell transplants independent of their locale by a simple blood test. We specifically studied a unique feature of cell transplant pharmacology—namely, immune clearance—using mesenchymal stromal cells (MSCs) as a proof-of-concept cell therapy. MSCs are a clinically relevant cell therapy that has been explored in several disease indications due to their innate properties of altering an immune response.

      Results

      Using this engineered reporter, we observed specific sensitivity of cell therapy exposure to the preparation of cells, cytolysis of MSCs in an allogeneic setting and a NK cell-mediated destruction of MSCs in an autologous setting.

      Conclusions

      Our cellular tracking method has broader implications at large for assessing in vivo kinetics of various other cell therapies.

      Key Words

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