Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke

Megan A. Evans; Rebecca Lim; Hyun Ah Kim; Hannah X. Chu; Chantelle V. Gardiner-Mann; Kimberly W.E. Taylor; Christopher T. Chan; Vanessa H. Brait; Seyoung Lee; Quynh Nhu Dinh; Antony Vinh; Thanh G. Phan; Velandai K. Srikanth; Henry Ma; Thiruma V. Arumugam; David Y. Fann; Luting Poh; Cameron P.J. Hunt; Colin W. Pouton; John M. Haynes; Stavros Selemidis; William Kwan; Leon Teo; James A. Bourne; Silke Neumann; Sarah Young; Emma K. Gowing; Grant R. Drummond; Andrew N. Clarkson; Euan M. Wallace; Christopher G. Sobey; Brad R.S. Broughton

doi:10.1161/STROKEAHA.117.019136

Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke

Megan A. Evans, Rebecca Lim, Hyun Ah Kim, Hannah X. Chu, Chantelle V. Gardiner-Mann, Kimberly W.E. Taylor, Christopher T. Chan, Vanessa H. Brait, Seyoung Lee, Quynh Nhu Dinh, Antony Vinh, Thanh G. Phan, Velandai K. Srikanth, Henry Ma, Thiruma V. Arumugam, David Y. Fann, Luting Poh, Cameron P.J. Hunt, Colin W. Pouton, John M. HaynesStavros Selemidis, William Kwan, Leon Teo, James A. Bourne, Silke Neumann, Sarah Young, Emma K. Gowing, Grant R. Drummond, Andrew N. Clarkson, Euan M. Wallace, Christopher G. Sobey, Brad R.S. Broughton

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

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Abstract

BACKGROUND AND PURPOSE: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke.

METHODS: We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex.

RESULTS: We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke.

CONCLUSIONS: Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.

Original language	English
Pages (from-to)	700-709
Number of pages	10
Journal	Stroke
Volume	49
Issue number	3
DOIs	https://doi.org/10.1161/STROKEAHA.117.019136
Publication status	Published - 1 Mar 2018

Keywords

brain ischemia
cerebral infarction
inflammation
mice
stem cells

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Evans, M. A., Lim, R., Kim, H. A., Chu, H. X., Gardiner-Mann, C. V., Taylor, K. W. E., Chan, C. T., Brait, V. H., Lee, S., Dinh, Q. N., Vinh, A., Phan, T. G., Srikanth, V. K., Ma, H., Arumugam, T. V., Fann, D. Y., Poh, L., Hunt, C. P. J., Pouton, C. W., ... Broughton, B. R. S. (2018). Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke. Stroke, 49(3), 700-709. https://doi.org/10.1161/STROKEAHA.117.019136

@article{4b04a0cec29b442d8b77009ef9b724b4,

title = "Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke",

abstract = "BACKGROUND AND PURPOSE: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke.METHODS: We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex.RESULTS: We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke.CONCLUSIONS: Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.",

keywords = "brain ischemia, cerebral infarction, inflammation, mice, stem cells",

author = "Evans, {Megan A.} and Rebecca Lim and Kim, {Hyun Ah} and Chu, {Hannah X.} and Gardiner-Mann, {Chantelle V.} and Taylor, {Kimberly W.E.} and Chan, {Christopher T.} and Brait, {Vanessa H.} and Seyoung Lee and Dinh, {Quynh Nhu} and Antony Vinh and Phan, {Thanh G.} and Srikanth, {Velandai K.} and Henry Ma and Arumugam, {Thiruma V.} and Fann, {David Y.} and Luting Poh and Hunt, {Cameron P.J.} and Pouton, {Colin W.} and Haynes, {John M.} and Stavros Selemidis and William Kwan and Leon Teo and Bourne, {James A.} and Silke Neumann and Sarah Young and Gowing, {Emma K.} and Drummond, {Grant R.} and Clarkson, {Andrew N.} and Wallace, {Euan M.} and Sobey, {Christopher G.} and Broughton, {Brad R.S.}",

year = "2018",

month = mar,

day = "1",

doi = "10.1161/STROKEAHA.117.019136",

language = "English",

volume = "49",

pages = "700--709",

journal = "Stroke",

issn = "0039-2499",

publisher = "American Heart Association",

number = "3",

}

Evans, MA, Lim, R, Kim, HA, Chu, HX, Gardiner-Mann, CV, Taylor, KWE, Chan, CT, Brait, VH, Lee, S, Dinh, QN, Vinh, A , Phan, TG , Srikanth, VK , Ma, H, Arumugam, TV, Fann, DY, Poh, L, Hunt, CPJ, Pouton, CW , Haynes, JM, Selemidis, S, Kwan, W , Teo, L, Bourne, JA, Neumann, S, Young, S, Gowing, EK, Drummond, GR, Clarkson, AN, Wallace, EM , Sobey, CG & Broughton, BRS 2018, 'Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke', Stroke, vol. 49, no. 3, pp. 700-709. https://doi.org/10.1161/STROKEAHA.117.019136

TY - JOUR

T1 - Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke

AU - Evans, Megan A.

AU - Lim, Rebecca

AU - Kim, Hyun Ah

AU - Chu, Hannah X.

AU - Gardiner-Mann, Chantelle V.

AU - Taylor, Kimberly W.E.

AU - Chan, Christopher T.

AU - Brait, Vanessa H.

AU - Lee, Seyoung

AU - Dinh, Quynh Nhu

AU - Vinh, Antony

AU - Phan, Thanh G.

AU - Srikanth, Velandai K.

AU - Ma, Henry

AU - Arumugam, Thiruma V.

AU - Fann, David Y.

AU - Poh, Luting

AU - Hunt, Cameron P.J.

AU - Pouton, Colin W.

AU - Haynes, John M.

AU - Selemidis, Stavros

AU - Kwan, William

AU - Teo, Leon

AU - Bourne, James A.

AU - Neumann, Silke

AU - Young, Sarah

AU - Gowing, Emma K.

AU - Drummond, Grant R.

AU - Clarkson, Andrew N.

AU - Wallace, Euan M.

AU - Sobey, Christopher G.

AU - Broughton, Brad R.S.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - BACKGROUND AND PURPOSE: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke.METHODS: We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex.RESULTS: We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke.CONCLUSIONS: Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.

AB - BACKGROUND AND PURPOSE: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke.METHODS: We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex.RESULTS: We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke.CONCLUSIONS: Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.

KW - brain ischemia

KW - cerebral infarction

KW - inflammation

KW - mice

KW - stem cells

UR - http://www.scopus.com/inward/record.url?scp=85042881596&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.117.019136

DO - 10.1161/STROKEAHA.117.019136

M3 - Article

C2 - 29382802

AN - SCOPUS:85042881596

VL - 49

SP - 700

EP - 709

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 3

ER -

Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke

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Keywords

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