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Interferon-gamma/Hypoxia Primed Mese...

Wobma, Holly.

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Interferon-gamma/Hypoxia Primed Mesenchymal Stem Cells for an Improved Immunosuppressive Cell Therapy.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Interferon-gamma/Hypoxia Primed Mesenchymal Stem Cells for an Improved Immunosuppressive Cell Therapy./
Author:	Wobma, Holly.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	113 p.
Notes:	Source: Dissertations Abstracts International, Volume: 79-11, Section: B.
Contained By:	Dissertations Abstracts International79-11B.
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10788340
ISBN:	9780355853209

Interferon-gamma/Hypoxia Primed Mesenchymal Stem Cells for an Improved Immunosuppressive Cell Therapy.
Wobma, Holly.

Interferon-gamma/Hypoxia Primed Mesenchymal Stem Cells for an Improved Immunosuppressive Cell Therapy. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 113 p.

Source: Dissertations Abstracts International, Volume: 79-11, Section: B.

Thesis (Ph.D.)--Columbia University, 2018.

This item must not be added to any third party search indexes.

Mesenchymal stem cells (MSCs) are promising candidates for treating diverse inflammatory disorders due to their capacity to be immunosuppressive. This phenotype is not present at baseline but develops in response to instructive cues. To date, clinical trials use cells grown in basic culture conditions, anticipating the cells will acquire a useful phenotype in response to in vivo cues. This strategy has failed to produce any FDA approved therapies, based on inconsistent efficacy. This thesis explores whether priming MSCs prior to administration can lead to a more uniformly therapeutic phenotype, and it details the design of an optimal in vitro priming regimen. Because interferon gamma (IFN-γ) is known to induce an anti-inflammatory state in MSCs, hypoxia can confer survival benefits, and both cues coexist in known situations of immune tolerance, we hypothesized dual IFN-γ/hypoxia priming would yield a superior immunosuppressive MSC therapy. We show that priming MSCs with hypoxia or IFN-γ alone improves their ability to inhibit T-cells in vitro, but combining these cues results in additive improvements. We next characterize the proteomic and metabolomic changes MSCs undergo when exposed to single or dual IFN-γ/hypoxia priming. While IFN-γ induces MSCs to suppress inflammation and fibrosis, hypoxia leads to cell adaptations to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. Dual priming results in additive effects, with many instances of synergy. Finally, we show initial evidence that dual primed MSCs are better able to inhibit disease progression in a mouse model of acute graft-vs-host disease (GvHD).

ISBN: 9780355853209Subjects--Topical Terms:

3172791
Cellular biology.

Interferon-gamma/Hypoxia Primed Mesenchymal Stem Cells for an Improved Immunosuppressive Cell Therapy.
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506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a Mesenchymal stem cells (MSCs) are promising candidates for treating diverse inflammatory disorders due to their capacity to be immunosuppressive. This phenotype is not present at baseline but develops in response to instructive cues. To date, clinical trials use cells grown in basic culture conditions, anticipating the cells will acquire a useful phenotype in response to in vivo cues. This strategy has failed to produce any FDA approved therapies, based on inconsistent efficacy. This thesis explores whether priming MSCs prior to administration can lead to a more uniformly therapeutic phenotype, and it details the design of an optimal in vitro priming regimen. Because interferon gamma (IFN-γ) is known to induce an anti-inflammatory state in MSCs, hypoxia can confer survival benefits, and both cues coexist in known situations of immune tolerance, we hypothesized dual IFN-γ/hypoxia priming would yield a superior immunosuppressive MSC therapy. We show that priming MSCs with hypoxia or IFN-γ alone improves their ability to inhibit T-cells in vitro, but combining these cues results in additive improvements. We next characterize the proteomic and metabolomic changes MSCs undergo when exposed to single or dual IFN-γ/hypoxia priming. While IFN-γ induces MSCs to suppress inflammation and fibrosis, hypoxia leads to cell adaptations to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. Dual priming results in additive effects, with many instances of synergy. Finally, we show initial evidence that dual primed MSCs are better able to inhibit disease progression in a mouse model of acute graft-vs-host disease (GvHD).
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