Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction

Abstract Despite widespread preclinical success, mesenchymal stromal cell (MSC) therapy has not reached consistent pivotal clinical endpoints in primary indications of autoinflammatory diseases. Numerous studies aim to uncover specific mechanisms of action towards better control of therapy using in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Matthew Li, Danika Khong, Ling-Yee Chin, Amy Singleton, Biju Parekkadan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/782a48001def412f8bfcf8ee08491cdc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:782a48001def412f8bfcf8ee08491cdc
record_format	dspace
spelling	oai:doaj.org-article:782a48001def412f8bfcf8ee08491cdc2021-12-02T12:32:35ZTherapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction10.1038/s41598-018-24971-22045-2322https://doaj.org/article/782a48001def412f8bfcf8ee08491cdc2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24971-2https://doaj.org/toc/2045-2322Abstract Despite widespread preclinical success, mesenchymal stromal cell (MSC) therapy has not reached consistent pivotal clinical endpoints in primary indications of autoinflammatory diseases. Numerous studies aim to uncover specific mechanisms of action towards better control of therapy using in vitro immunomodulation assays. However, many of these immunomodulation assays are imperfectly designed to accurately recapitulate microenvironment conditions where MSCs act. To increase our understanding of MSC efficacy, we herein conduct a systems level microenvironment approach to define compartmental features that can influence the delivery of MSCs’ immunomodulatory effect in vitro in a more quantitative manner than ever before. Using this approach, we notably uncover an improved MSC quantification method with predictive cross-study applicability and unveil the key importance of system volume, time exposure to MSCs, and cross-communication between MSC and T cell populations to realize full therapeutic effect. The application of these compartmental analysis can improve our understanding of MSC mechanism(s) of action and further lead to administration methods that deliver MSCs within a compartment for predictable potency.Matthew LiDanika KhongLing-Yee ChinAmy SingletonBiju ParekkadanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew Li Danika Khong Ling-Yee Chin Amy Singleton Biju Parekkadan Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
description	Abstract Despite widespread preclinical success, mesenchymal stromal cell (MSC) therapy has not reached consistent pivotal clinical endpoints in primary indications of autoinflammatory diseases. Numerous studies aim to uncover specific mechanisms of action towards better control of therapy using in vitro immunomodulation assays. However, many of these immunomodulation assays are imperfectly designed to accurately recapitulate microenvironment conditions where MSCs act. To increase our understanding of MSC efficacy, we herein conduct a systems level microenvironment approach to define compartmental features that can influence the delivery of MSCs’ immunomodulatory effect in vitro in a more quantitative manner than ever before. Using this approach, we notably uncover an improved MSC quantification method with predictive cross-study applicability and unveil the key importance of system volume, time exposure to MSCs, and cross-communication between MSC and T cell populations to realize full therapeutic effect. The application of these compartmental analysis can improve our understanding of MSC mechanism(s) of action and further lead to administration methods that deliver MSCs within a compartment for predictable potency.
format	article
author	Matthew Li Danika Khong Ling-Yee Chin Amy Singleton Biju Parekkadan
author_facet	Matthew Li Danika Khong Ling-Yee Chin Amy Singleton Biju Parekkadan
author_sort	Matthew Li
title	Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
title_short	Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
title_full	Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
title_fullStr	Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
title_full_unstemmed	Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction
title_sort	therapeutic delivery specifications identified through compartmental analysis of a mesenchymal stromal cell-immune reaction
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/782a48001def412f8bfcf8ee08491cdc
work_keys_str_mv	AT matthewli therapeuticdeliveryspecificationsidentifiedthroughcompartmentalanalysisofamesenchymalstromalcellimmunereaction AT danikakhong therapeuticdeliveryspecificationsidentifiedthroughcompartmentalanalysisofamesenchymalstromalcellimmunereaction AT lingyeechin therapeuticdeliveryspecificationsidentifiedthroughcompartmentalanalysisofamesenchymalstromalcellimmunereaction AT amysingleton therapeuticdeliveryspecificationsidentifiedthroughcompartmentalanalysisofamesenchymalstromalcellimmunereaction AT bijuparekkadan therapeuticdeliveryspecificationsidentifiedthroughcompartmentalanalysisofamesenchymalstromalcellimmunereaction
_version_	1718394042158415872

Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction

Ejemplares similares