Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells

Abstract Mesenchymal stem cell (MSC)-based therapy has shown great promises in various animal disease models. However, this therapeutic potency has not been well claimed when applied to human clinical trials. This is due to both the availability of MSCs at the time of administration and lack of viab...

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Autores principales:	Brent M. Bijonowski, Xuegang Yuan, Richard Jeske, Yan Li, Samuel C. Grant
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/482015429f474ea69540a7f3390f307c
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spelling	oai:doaj.org-article:482015429f474ea69540a7f3390f307c2021-12-02T12:33:54ZCyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells10.1038/s41598-020-77288-42045-2322https://doaj.org/article/482015429f474ea69540a7f3390f307c2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77288-4https://doaj.org/toc/2045-2322Abstract Mesenchymal stem cell (MSC)-based therapy has shown great promises in various animal disease models. However, this therapeutic potency has not been well claimed when applied to human clinical trials. This is due to both the availability of MSCs at the time of administration and lack of viable expansion strategies. MSCs are very susceptible to in vitro culture environment and tend to adapt the microenvironment which could lead to cellular senescence and aging. Therefore, extended in vitro expansion induces loss of MSC functionality and its clinical relevance. To combat this effect, this work assessed a novel cyclical aggregation as a means of expanding MSCs to maintain stem cell functionality. The cyclical aggregation consists of an aggregation phase and an expansion phase by replating the dissociated MSC aggregates onto planar tissue culture surfaces. The results indicate that cyclical aggregation maintains proliferative capability, stem cell proteins, and clonogenicity, and prevents the acquisition of senescence. To determine why aggregation was responsible for this phenomenon, the integrated stress response pathway was probed with salubrial and GSK-2606414. Treatment with salubrial had no significant effect, while GSK-2606414 mitigated the effects of aggregation leading to in vitro aging. This method holds the potential to increase the clinical relevance of MSC therapeutic effects from small model systems (such as rats and mice) to humans, and may open the potential of patient-derived MSCs for treatment thereby removing the need for immunosuppression.Brent M. BijonowskiXuegang YuanRichard JeskeYan LiSamuel C. GrantNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brent M. Bijonowski Xuegang Yuan Richard Jeske Yan Li Samuel C. Grant Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
description	Abstract Mesenchymal stem cell (MSC)-based therapy has shown great promises in various animal disease models. However, this therapeutic potency has not been well claimed when applied to human clinical trials. This is due to both the availability of MSCs at the time of administration and lack of viable expansion strategies. MSCs are very susceptible to in vitro culture environment and tend to adapt the microenvironment which could lead to cellular senescence and aging. Therefore, extended in vitro expansion induces loss of MSC functionality and its clinical relevance. To combat this effect, this work assessed a novel cyclical aggregation as a means of expanding MSCs to maintain stem cell functionality. The cyclical aggregation consists of an aggregation phase and an expansion phase by replating the dissociated MSC aggregates onto planar tissue culture surfaces. The results indicate that cyclical aggregation maintains proliferative capability, stem cell proteins, and clonogenicity, and prevents the acquisition of senescence. To determine why aggregation was responsible for this phenomenon, the integrated stress response pathway was probed with salubrial and GSK-2606414. Treatment with salubrial had no significant effect, while GSK-2606414 mitigated the effects of aggregation leading to in vitro aging. This method holds the potential to increase the clinical relevance of MSC therapeutic effects from small model systems (such as rats and mice) to humans, and may open the potential of patient-derived MSCs for treatment thereby removing the need for immunosuppression.
format	article
author	Brent M. Bijonowski Xuegang Yuan Richard Jeske Yan Li Samuel C. Grant
author_facet	Brent M. Bijonowski Xuegang Yuan Richard Jeske Yan Li Samuel C. Grant
author_sort	Brent M. Bijonowski
title	Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
title_short	Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
title_full	Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
title_fullStr	Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
title_full_unstemmed	Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
title_sort	cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/482015429f474ea69540a7f3390f307c
work_keys_str_mv	AT brentmbijonowski cyclicalaggregationextendsinvitroexpansionpotentialofhumanmesenchymalstemcells AT xuegangyuan cyclicalaggregationextendsinvitroexpansionpotentialofhumanmesenchymalstemcells AT richardjeske cyclicalaggregationextendsinvitroexpansionpotentialofhumanmesenchymalstemcells AT yanli cyclicalaggregationextendsinvitroexpansionpotentialofhumanmesenchymalstemcells AT samuelcgrant cyclicalaggregationextendsinvitroexpansionpotentialofhumanmesenchymalstemcells
_version_	1718393855713214464

Cyclical aggregation extends in vitro expansion potential of human mesenchymal stem cells

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