Amy Singleton1, Danika Khong1, Ling-Yee Chin1, Shilpaa Mukundan1, Matthew Li1, Biju Parekkadan2. 1. 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. 2. 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. Electronic address: biju_parekkadan@hms.harvard.edu.
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.
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.
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