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 & 12 others 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

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Pages (from-to)700-709
Number of pages10
JournalStroke
Volume49
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • brain ischemia
  • cerebral infarction
  • inflammation
  • mice
  • stem cells

Cite this

Evans, Megan A. ; Lim, Rebecca ; Kim, Hyun Ah ; Chu, Hannah X. ; Gardiner-Mann, Chantelle V. ; Taylor, Kimberly W.E. ; Chan, Christopher T. ; Brait, Vanessa H. ; Lee, Seyoung ; Dinh, Quynh Nhu ; Vinh, Antony ; Phan, Thanh G. ; Srikanth, Velandai K. ; Ma, Henry ; Arumugam, Thiruma V. ; Fann, David Y. ; Poh, Luting ; Hunt, Cameron P.J. ; Pouton, Colin W. ; Haynes, John M. ; Selemidis, Stavros ; Kwan, William ; Teo, Leon ; Bourne, James A. ; Neumann, Silke ; Young, Sarah ; Gowing, Emma K. ; Drummond, Grant R. ; Clarkson, Andrew N. ; Wallace, Euan M. ; Sobey, Christopher G. ; Broughton, Brad R.S. / Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke. In: Stroke. 2018 ; Vol. 49, No. 3. pp. 700-709.
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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.}",
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Acute or Delayed Systemic Administration of Human Amnion Epithelial Cells Improves Outcomes in Experimental Stroke. / Evans, Megan A.; Lim, Rebecca; Kim, Hyun Ah; Chu, Hannah X.; Gardiner-Mann, Chantelle V.; Taylor, Kimberly W.E.; Chan, Christopher T.; Brait, Vanessa H.; Lee, Seyoung; Dinh, Quynh Nhu; Vinh, Antony; Phan, Thanh G.; Srikanth, Velandai K.; Ma, Henry; Arumugam, Thiruma V.; Fann, David Y.; Poh, Luting; Hunt, Cameron P.J.; Pouton, Colin W.; Haynes, John M.; Selemidis, Stavros; Kwan, William; Teo, Leon; Bourne, James A.; Neumann, Silke; Young, Sarah; Gowing, Emma K.; Drummond, Grant R.; Clarkson, Andrew N.; Wallace, Euan M.; Sobey, Christopher G.; Broughton, Brad R.S.

In: Stroke, Vol. 49, No. 3, 01.03.2018, p. 700-709.

Research output: Contribution to journalArticleResearchpeer-review

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

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U2 - 10.1161/STROKEAHA.117.019136

DO - 10.1161/STROKEAHA.117.019136

M3 - Article

VL - 49

SP - 700

EP - 709

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 3

ER -