title: The efficacy of extraembryonic stem cells in improving blood flow within animal models of lower limb ischaemia.
abstract: BACKGROUND
  Stem cell (SC) administration is a potential therapeutic strategy to improve blood supply in patients with peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to investigate the efficacy of extraembryonic tissue-derived SC (ETSC) in improving blood flow within animal models of hindlimb ischaemia (HLI).
  
  
  METHODS
  PubMed, ScienceDirect and Web of Science were searched to identify studies which investigated ETSCs within animal HLI models. A meta-analysis was performed focusing on the effect of ETSCs on limb blood flow assessed by laser Doppler imaging using a random effects model. Methodological quality was assessed using a newly devised quality assessment tool.
  
  
  RESULTS
  Five studies investigating umbilical cord-derived SCs (three studies), placental SCs (one study), amnion and chorionic SCs (one study) were included. A meta-analysis suggested that administration of ETSCs improved the restoration of blood flow within the HLI models used. The methodological quality of the included studies was assessed as poor. Problems identified included lack of randomised design and blinding of outcome assessors; that the animal models did not incorporate recognised risk factors for human PAD or atherosclerosis; the models used did not have established chronic ischaemia as is the cases in most patients presenting with PAD; and the studies lacked a clear rationale for the dosage and frequency of SCs administered.
  
  
  CONCLUSIONS
  The identified studies suggest that ETSCs improve recovery of limb blood supply within current animal HLI models. Improved study quality is, however, needed to provide support for the likelihood of translating these findings to patients with PAD.
authors.affiliation: Queensland Research Centre for Peripheral Vascular Diseases, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
authors.forename: Safraz
authors.initials: S
authors.lastname: Mohamed Omer
authors.affiliation: Queensland Research Centre for Peripheral Vascular Diseases, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
authors.forename: Smriti Murali
authors.identifier: http://orcid.org/0000-0002-0810-5144
authors.initials: SM
authors.lastname: Krishna
authors.affiliation: Queensland Research Centre for Peripheral Vascular Diseases, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
authors.forename: Jiaze
authors.initials: J
authors.lastname: Li
authors.affiliation: Queensland Research Centre for Peripheral Vascular Diseases, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
authors.forename: Joseph Vaughan
authors.identifier: http://orcid.org/0000-0002-2131-2068
authors.initials: JV
authors.lastname: Moxon
authors.affiliation: Queensland Research Centre for Peripheral Vascular Diseases, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
authors.forename: Vianne
authors.initials: V
authors.lastname: Nsengiyumva
authors.affiliation: Queensland Research Centre for Peripheral Vascular Diseases, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000502:physiology / Q000637:transplantation*; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D018482:Muscle, Skeletal / Q000098:blood supply*; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D010641:Phenotype; D020127:Recovery of Function; D012039:Regional Blood Flow; D033581:Stem Cell Transplantation