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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bebf5db53a4d4a56accd59d2bbe8606b
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spelling	oai:doaj.org-article:bebf5db53a4d4a56accd59d2bbe8606b2021-11-18T08:31:25ZPharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells.1932-620310.1371/journal.pone.0089882https://doaj.org/article/bebf5db53a4d4a56accd59d2bbe8606b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587097/?tool=EBIhttps://doaj.org/toc/1932-6203Transient 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.Jessica S ElmanRyan C MurrayFangjing WangKeyue ShenShan GaoKevin E ConwayMartin L YarmushBakhos A TannousRalph WeisslederBiju ParekkadanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89882 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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.
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.
format	article
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
title	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_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_sort	pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/bebf5db53a4d4a56accd59d2bbe8606b
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Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells.

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