Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells.
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587097/?tool=EBI |
| _version_ | 1818337530201767936 |
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| author | Jessica S Elman Ryan C Murray Fangjing Wang Keyue Shen Shan Gao Kevin E Conway Martin L Yarmush Bakhos A Tannous Ralph Weissleder Biju Parekkadan |
| author_facet | Jessica S Elman Ryan C Murray Fangjing Wang Keyue Shen Shan Gao Kevin E Conway Martin L Yarmush Bakhos A Tannous Ralph Weissleder Biju Parekkadan |
| author_sort | Jessica S Elman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T14:56:41Z |
| format | Article |
| id | doaj.art-bebf5db53a4d4a56accd59d2bbe8606b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T14:56:41Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bebf5db53a4d4a56accd59d2bbe8606b2022-12-21T23:41:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8988210.1371/journal.pone.0089882Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells.Jessica S ElmanRyan C MurrayFangjing WangKeyue ShenShan GaoKevin E ConwayMartin L YarmushBakhos A TannousRalph WeisslederBiju ParekkadanTransient 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587097/?tool=EBI |
| spellingShingle | Jessica S Elman Ryan C Murray Fangjing Wang Keyue Shen Shan Gao Kevin E Conway Martin L Yarmush Bakhos A Tannous Ralph Weissleder Biju Parekkadan Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. PLoS ONE |
| title | Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. |
| title_full | Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. |
| title_fullStr | Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. |
| title_full_unstemmed | Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. |
| title_short | Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. |
| title_sort | pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587097/?tool=EBI |
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