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

Jessica S. Elman, Ryan M. Murray, Fangjing Wang, Keyue Shen, Shan Gao, Kevin E. Conway, Martin L. Yarmush, Bakhos A. Tannous, Ralph Weissleder, Biju Parekkadan

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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 antiinflammatory 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.

Original languageEnglish (US)
Article numbere89882
JournalPloS one
Issue number2
StatePublished - Feb 21 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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