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

Stroke. 2018 Mar;49(3):700-709. doi: 10.1161/STROKEAHA.117.019136. Epub 2018 Jan 30.

Authors

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

Affiliations

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.

PMID: 29382802
DOI: 10.1161/STROKEAHA.117.019136

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amnion / transplantation*
Animals
Callithrix
Disease Models, Animal
Epithelial Cells / transplantation*
Female
Heterografts
Humans
Male
Mice
Neuroprotection*
Stroke / metabolism
Stroke / pathology
Stroke / therapy*