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

Elman JS, Murray RC, Wang F, Shen K, Gao S, Conway KE, Yarmush ML, Tannous BA, Weissleder R4, Parekkadan B
Source: PLoS ONE
Publication Date: (2014)
Issue: 9(2): ePub
Research Area:
Stem Cells
Basic Research
Cells used in publication:
Mesenchymal stem cell (MSC), human
Species: human
Tissue Origin: bone marrow
Bone Marrow, Human, Unprocessed
Species: human
Tissue Origin: bone marrow
Mononuclear, bone marrow, human
Species: human
Tissue Origin: bone marrow
Culture Media:
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.