Megan A Evans1, Rebecca Lim1, Hyun Ah Kim1, Hannah X Chu1, Chantelle V Gardiner-Mann1, Kimberly W E Taylor1, Christopher T Chan1, Vanessa H Brait1, Seyoung Lee1, Quynh Nhu Dinh1, Antony Vinh1, Thanh G Phan1, Velandai K Srikanth1, Henry Ma1, Thiruma V Arumugam1, David Y Fann1, Luting Poh1, Cameron P J Hunt1, Colin W Pouton1, John M Haynes1, Stavros Selemidis1, William Kwan1, Leon Teo1, James A Bourne1, Silke Neumann1, Sarah Young1, Emma K Gowing1, Grant R Drummond1, Andrew N Clarkson1, Euan M Wallace1, Christopher G Sobey2, Brad R S Broughton1. 1. From the Departments of Pharmacology (M.A.E., H.A.K., H.X.C., C.V.G.-M., K.W.E.T., C.T.C., V.H.B., S.L., Q.N.D., A.V., G.R.D., C.G.S., B.R.S.B.), Obstetrics and Gynaecology (R.L., E.M.W.), Surgery (A.V., G.R.D., C.G.S.), and Medicine (T.G.P., V.K.S.), Australian Regenerative Medicine Institute (W.K., L.T., J.A.B.), and Monash Institute of Pharmaceutical Sciences (C.P.J.H., C.W.P., J.M.H.), Monash University, Victoria, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Victoria, Australia (M.A.E., H.A.K., Q.N.D., A.V., G.R.D., C.G.S.); The Ritchie Centre, Hudson Institute of Medical Research, Victoria, Australia (R.L., E.M.W.); Stroke Unit (T.G.P., V.K.S., H.M.) and Monash Women's Services (E.M.W.), Monash Health, Victoria, Australia; Menzies Research Institute, Tasmania, Australia (V.K.S.); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (T.V.A., D.Y.F., L.P.); School of Pharmacy, Sungkyunkwan University, Seoul, South Korea (T.V.A.); School of Health and Biomedical Sciences, RMIT University, Victoria, Australia (S.S.); Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand (S.N., E.K.G., A.N.C.) and Department of Pathology (S.N.;S.Y.;A.N.C.), University of Otago, Dunedin, New Zealand; and Faculty of Pharmacy, University of Sydney, NSW, Australia (A.N.C.). 2. From the Departments of Pharmacology (M.A.E., H.A.K., H.X.C., C.V.G.-M., K.W.E.T., C.T.C., V.H.B., S.L., Q.N.D., A.V., G.R.D., C.G.S., B.R.S.B.), Obstetrics and Gynaecology (R.L., E.M.W.), Surgery (A.V., G.R.D., C.G.S.), and Medicine (T.G.P., V.K.S.), Australian Regenerative Medicine Institute (W.K., L.T., J.A.B.), and Monash Institute of Pharmaceutical Sciences (C.P.J.H., C.W.P., J.M.H.), Monash University, Victoria, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Victoria, Australia (M.A.E., H.A.K., Q.N.D., A.V., G.R.D., C.G.S.); The Ritchie Centre, Hudson Institute of Medical Research, Victoria, Australia (R.L., E.M.W.); Stroke Unit (T.G.P., V.K.S., H.M.) and Monash Women's Services (E.M.W.), Monash Health, Victoria, Australia; Menzies Research Institute, Tasmania, Australia (V.K.S.); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (T.V.A., D.Y.F., L.P.); School of Pharmacy, Sungkyunkwan University, Seoul, South Korea (T.V.A.); School of Health and Biomedical Sciences, RMIT University, Victoria, Australia (S.S.); Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand (S.N., E.K.G., A.N.C.) and Department of Pathology (S.N.;S.Y.;A.N.C.), University of Otago, Dunedin, New Zealand; and Faculty of Pharmacy, University of Sydney, NSW, Australia (A.N.C.). c.sobey@latrobe.edu.au.
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.
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.
Authors: Fraser Nott; J Jane Pillow; MarJanna Dahl; Sharmony B Kelly; Jacqueline Melville; Courtney McDonald; Ilias Nitsos; Rebecca Lim; Euan M Wallace; Graham Jenkin; Graeme R Polglase; Timothy J Moss; Robert Galinsky Journal: Pediatr Res Date: 2020-03-02 Impact factor: 3.756
Authors: Salomon Poliwoda; Nazir Noor; Evan Downs; Amanda Schaaf; Abigail Cantwell; Latha Ganti; Alan D Kaye; Luke I Mosel; Caroline B Carroll; Omar Viswanath; Ivan Urits Journal: Orthop Rev (Pavia) Date: 2022-08-25
Authors: Megan A Evans; Hyun Ah Kim; Yeong Hann Ling; Sandy Uong; Antony Vinh; T Michael De Silva; Thiruma V Arumugam; Andrew N Clarkson; Graeme R Zosky; Grant R Drummond; Brad R S Broughton; Christopher G Sobey Journal: Neuromolecular Med Date: 2018-02-23 Impact factor: 3.843
Authors: Megan A Evans; Brad R S Broughton; Grant R Drummond; Henry Ma; Thanh G Phan; Euan M Wallace; Rebecca Lim; Christopher G Sobey Journal: Neural Regen Res Date: 2018-08 Impact factor: 5.135