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Acute or delayed systemic administration of human amnion epithelial cells improves outcomes in experimental stroke

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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 and 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 , doi: https://doi.org/10.1161/STROKEAHA.117.019136.

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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.

Item Type:	Article
Authors/Creators:	Evans, MA and Lim, R and Kim, HA and Chu, HX and Gardiner-Mann, CV and Taylor, KWE and Chan, CT and Brait, VH and Lee, S and Dinh, QN and Vinh, A and Phan, TG and Srikanth, VK and Ma, H and Arumugam, TV and Fann, DY and Poh, L and Hunt, CPJ and Pouton, CW and Haynes, JM and Selemidis, S and Kwan, W and Teo, L and Bourne, JA and Neumann, S and Young, S and Gowing, EK and Drummond, GR and Clarkson, AN and Wallace, EM and Sobey, CG and Broughton, BRS
Keywords:	brain ischemia, cerebral infarction, inflammation, mice, stem cells
Journal or Publication Title:	Stroke
Publisher:	Lippincott Williams & Wilkins
ISSN:	0039-2499
DOI / ID Number:	https://doi.org/10.1161/STROKEAHA.117.019136
Copyright Information:	Copyright 2018 American Heart Association, Inc.
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