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PLoS One. 2014 Feb 21;9(2):e89882. doi: 10.1371/journal.pone.0089882. eCollection 2014.

Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells.

Author information

  • 1Department of Surgery, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospital for Children, Boston, Massachusetts, United States of America.
  • 2Department of Neurology, Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
  • 3Department of Surgery, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospital for Children, Boston, Massachusetts, United States of America ; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America.
  • 4Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
  • 5Department of Surgery, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospital for Children, Boston, Massachusetts, United States of America ; Harvard Stem Cell Institute, Boston, Massachusetts, United States of America.

Abstract

Transient cell therapy is an emerging drug class that requires new approaches for pharmacological monitoring during use. Human mesenchymal stem cells (MSCs) are a clinically-tested transient cell therapeutic that naturally secrete anti-inflammatory factors to attenuate immune-mediated diseases. MSCs were used as a proof-of-concept with the hypothesis that measuring the release of secreted factors after cell transplantation, rather than the biodistribution of the cells alone, would be an alternative monitoring tool to understand the exposure of a subject to MSCs. By comparing cellular engraftment and the associated serum concentration of secreted factors released from the graft, we observed clear differences between the pharmacokinetics of MSCs and their secreted factors. Exploration of the effects of natural or engineered secreted proteins, active cellular secretion pathways, and clearance mechanisms revealed novel aspects that affect the systemic exposure of the host to secreted factors from a cellular therapeutic. We assert that a combined consideration of cell delivery strategies and molecular pharmacokinetics can provide a more predictive model for outcomes of MSC transplantation and potentially other transient cell therapeutics.

PMID:
24587097
[PubMed - indexed for MEDLINE]
PMCID:
PMC3931832
Free PMC Article
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