Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

Catriona J Cunningham; Raymond Wong; Jack Barrington; Sabrina Tamburrano; Emmanuel Pinteaux; Stuart M. Allan

doi:10.1186/s13287-020-1560-y

Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

Catriona J Cunningham, Raymond Wong, Jack Barrington, Sabrina Tamburrano, Emmanuel Pinteaux, Stuart M. Allan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

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Abstract

Background
Mesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles—collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1α-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia.

Methods
Stroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.

Results
IL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke.

Conclusions
Our results show for the first time that the administration of conditioned medium from IL-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.

Original language	English
Article number	32
Journal	Stem cell research & therapy
Volume	11
DOIs	https://doi.org/10.1186/s13287-020-1560-y
Publication status	Published - 21 Jan 2020

Keywords

cell therapy
conditioned medium
mesenchymal stem cell
secretome
stroke
Mesenchymal stem cell
Stroke
Cell therapy
Conditioned medium
Secretome
FUNCTIONAL RECOVERY
BEHAVIOR
MODEL
NEUROPROTECTION
TRANSPLANTATION
INFLAMMATION
THERAPEUTIC BENEFIT
CEREBRAL-ISCHEMIA
BRAIN
MARROW STROMAL CELLS

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10.1186/s13287-020-1560-yLicence: CC BY

Cunningham_etal_SCRT_Systemic_conditioned_VOR
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 1.63 MBLicence: CC BY

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@article{2eb42bf0aacb48ac9c55a45ca9cc9727,

title = "Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke",

abstract = "BackgroundMesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles—collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1α-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia.MethodsStroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.ResultsIL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke.ConclusionsOur results show for the first time that the administration of conditioned medium from IL-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.",

keywords = "cell therapy, conditioned medium, mesenchymal stem cell, secretome, stroke, Mesenchymal stem cell, Stroke, Cell therapy, Conditioned medium, Secretome, FUNCTIONAL RECOVERY, BEHAVIOR, MODEL, NEUROPROTECTION, TRANSPLANTATION, INFLAMMATION, THERAPEUTIC BENEFIT, CEREBRAL-ISCHEMIA, BRAIN, MARROW STROMAL CELLS",

author = "Cunningham, {Catriona J} and Raymond Wong and Jack Barrington and Sabrina Tamburrano and Emmanuel Pinteaux and Allan, {Stuart M.}",

note = "This work was supported by the Engineering and Physical Sciences Research Council (EPSRC, UK) and Medical Research Council (MRC, UK) Centre for Doctoral Training in Regenerative Medicine studentship grant EP/L014904/1 and the Stroke Association (TSA 2017/03). ",

year = "2020",

month = jan,

day = "21",

doi = "10.1186/s13287-020-1560-y",

language = "English",

volume = "11",

journal = "Stem cell research & therapy",

issn = "1757-6512",

publisher = "BioMed Central",

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TY - JOUR

T1 - Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

AU - Cunningham, Catriona J

AU - Wong, Raymond

AU - Barrington, Jack

AU - Tamburrano, Sabrina

AU - Pinteaux, Emmanuel

AU - Allan, Stuart M.

N1 - This work was supported by the Engineering and Physical Sciences Research Council (EPSRC, UK) and Medical Research Council (MRC, UK) Centre for Doctoral Training in Regenerative Medicine studentship grant EP/L014904/1 and the Stroke Association (TSA 2017/03).

PY - 2020/1/21

Y1 - 2020/1/21

N2 - BackgroundMesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles—collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1α-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia.MethodsStroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.ResultsIL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke.ConclusionsOur results show for the first time that the administration of conditioned medium from IL-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.

AB - BackgroundMesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles—collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1α-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia.MethodsStroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.ResultsIL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke.ConclusionsOur results show for the first time that the administration of conditioned medium from IL-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.

KW - cell therapy

KW - conditioned medium

KW - mesenchymal stem cell

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KW - stroke

KW - Mesenchymal stem cell

KW - Stroke

KW - Cell therapy

KW - Conditioned medium

KW - Secretome

KW - FUNCTIONAL RECOVERY

KW - BEHAVIOR

KW - MODEL

KW - NEUROPROTECTION

KW - TRANSPLANTATION

KW - INFLAMMATION

KW - THERAPEUTIC BENEFIT

KW - CEREBRAL-ISCHEMIA

KW - BRAIN

KW - MARROW STROMAL CELLS

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U2 - 10.1186/s13287-020-1560-y

DO - 10.1186/s13287-020-1560-y

M3 - Article

VL - 11

JO - Stem cell research & therapy

JF - Stem cell research & therapy

SN - 1757-6512

M1 - 32

ER -

Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

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