title: Amniotic fluid stem cells are cardioprotective following acute myocardial infarction.
abstract: In recent years, various types of stem cells have been characterized and their potential for cardiac regeneration has been investigated. We have previously described the isolation of broadly multipotent cells from amniotic fluid, defined as amniotic fluid stem (AFS) cells. The aim of this study was to investigate the therapeutic potential of human AFS cells (hAFS) in a model of acute myocardial infarction. Wistar rats underwent 30 min of ischemia by ligation of the left anterior descending coronary artery, followed by administration of hAFS cells and 2 h of reperfusion. Infarct size was assessed by 2,3,5-triphenyltetrazolium chloride staining and planimetry. hAFS cells were also analyzed by enzyme-linked immunosorbent assay to detect secretion of putative paracrine factors, such as the actin monomer-binding protein thymosin β4 (Tβ4). The systemic injection of hAFS cells and their conditioned medium (hAFS-CM) was cardioprotective, improving myocardial cell survival and decreasing the infarct size from 53.9%±2.3% (control animals receiving phosphate-buffered saline injection) to 40.0%±3.0% (hAFS cells) and 39.7%±2.5% (hAFS-CM, P<0.01). In addition, hAFS cells were demonstrated to secrete Tβ4, previously shown to be both cardioprotective and proangiogenic. Our results suggest that AFS cells have therapeutic potential in the setting of acute myocardial infarction, which may be mediated through paracrine effectors such as Tβ4. Therefore, AFS cells might represent a novel source for cell therapy and cell transplantation strategies in repair following ischemic heart disease, with a possible paracrine mechanism of action and a potential molecular candidate for acute cardioprotection.
authors.affiliation: Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, London, UK.
authors.forename: Sveva
authors.initials: S
authors.lastname: Bollini
authors.forename: King K
authors.initials: KK
authors.lastname: Cheung
authors.forename: Johannes
authors.initials: J
authors.lastname: Riegler
authors.forename: Xuebin
authors.initials: X
authors.lastname: Dong
authors.forename: Nicola
authors.initials: N
authors.lastname: Smart
authors.forename: Marco
authors.initials: M
authors.lastname: Ghionzoli
authors.forename: Stavros P
authors.initials: SP
authors.lastname: Loukogeorgakis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Maghsoudlou
authors.forename: Karina N
authors.initials: KN
authors.lastname: Dubé
authors.forename: Paul R
authors.initials: PR
authors.lastname: Riley
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013947:Thymosin / Q000378:metabolism*; D000099201:Thymosin beta(4)
chemical_list: D000943:Antigens, Differentiation; D013947:Thymosin; D000099201:Thymosin beta(4)