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

被引：62

作者：

Evans, Megan A. ^{[1
,7
]}

Lim, Rebecca ^{[2
,8
]}

Kim, Hyun Ah ^{[1
,7
]}

Chu, Hannah X. ^{[1
]}

Gardiner-Mann, Chantelle V. ^{[1
]}

Taylor, Kimberly W. E. ^{[1
]}

Chan, Christopher T. ^{[1
]}

Brait, Vanessa H. ^{[1
]}

Lee, Seyoung ^{[1
]}

Quynh Nhu Dinh ^{[1
,7
]}

Vinh, Antony ^{[1
,3
,7
]}

Phan, Thanh G. ^{[4
,9
]}

Srikanth, Velandai K. ^{[4
,9
,11
]}

Ma, Henry ^{[9
]}

Arumugam, Thiruma V. ^{[12
,13
]}

Fann, David Y. ^{[12
]}

Poh, Luting ^{[12
]}

Hunt, Cameron P. J. ^{[6
]}

Pouton, Colin W. ^{[6
]}

Haynes, John M. ^{[6
]}

Selemidis, Stavros ^{[14
]}

Kwan, William ^{[5
]}

Teo, Leon ^{[5
]}

Bourne, James A. ^{[5
]}

Neumann, Silke ^{[15
,16
,17
]}

Young, Sarah ^{[17
]}

Gowing, Emma K. ^{[15
,16
]}

Drummond, Grant R. ^{[1
,3
,7
]}

Clarkson, Andrew N. ^{[15
,16
,17
,18
]}

Wallace, Euan M. ^{[2
,8
,10
]}

Sobey, Christopher G. ^{[1
,3
,7
]}

Broughton, Brad R. S. ^{[1
]}

机构：

[1] Monash Univ, Dept Pharmacol, Clayton, Vic, Australia

[2] Monash Univ, Dept Obstet & Gynaecol, Clayton, Vic, Australia

[3] Monash Univ, Dept Surg, Clayton, Vic, Australia

[4] Monash Univ, Dept Med, Clayton, Vic, Australia

[5] Monash Univ, Australian Regenerat Med Inst, Clayton, Vic, Australia

[6] Monash Univ, Monash Inst Pharmaceut Sci, Clayton, Vic, Australia

[7] La Trobe Univ, Dept Physiol Anat & Microbiol, Bundoora, Vic, Australia

[8] Hudson Inst Med Res, Ritchie Ctr, Clayton, Vic, Australia

[9] Monash Hlth, Stroke Unit, Dandenong, Vic, Australia

[10] Monash Hlth, Monash Womens Serv, Dandenong, Vic, Australia

[11] Menzies Res Inst, Hobart, Tas, Australia

[12] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore, Singapore

[13] Sungkyunkwan Univ, Sch Pharm, Seoul, South Korea

[14] RMIT Univ, Sch Hlth & Biomed Sci, Melbourne, Vic, Australia

[15] Univ Otago, Brain Hlth Res Ctr, Dept Anat, Dunedin, New Zealand

[16] Univ Otago, Brain Res New Zealand, Dunedin, New Zealand

[17] Univ Otago, Dept Pathol, Dunedin, New Zealand

[18] Univ Sydney, Fac Pharm, Sydney, NSW, Australia

来源：

STROKE | 2018年 / 49卷 / 03期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

brain ischemia; cerebral infarction; inflammation; mice; stem cells; TRANSPLANTATION; INFLAMMATION; ISCHEMIA; THERAPY; SPLEEN; BLOOD; MODEL;

D O I：

10.1161/STROKEAHA.117.019136

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：700 / 709

页数：10

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