title: Alginate microencapsulation of human mesenchymal stem cells as a strategy to enhance paracrine-mediated vascular recovery after hindlimb ischaemia.
abstract: Stem cell-based therapies hold great promise as a clinically viable approach for vascular regeneration. Preclinical studies have been very encouraging and early clinical trials have suggested favourable outcomes. However, significant challenges remain in terms of optimizing cell retention and maintenance of the paracrine effects of implanted cells. To address these issues, we have proposed the use of a cellular encapsulation approach to enhance vascular regeneration. We contained human mesenchymal stem cells (hMSCs) in biocompatible alginate microcapsules for therapeutic treatment in the setting of murine hindlimb ischaemia. This approach supported the paracrine pro-angiogenic activity of hMSCs, prevented incorporation of hMSCs into the host tissue and markedly enhanced their therapeutic effect. While injection of non-encapsulated hMSCs resulted in a 22 ± 10% increase in vascular density and no increase in perfusion, treatment with encapsulated hMSCs resulted in a 70 ± 8% increase in vascular density and 21 ± 7% increase in perfusion. The described cellular encapsulation strategy may help to better define the mechanisms responsible for the beneficial effects of cell-based therapies and provide a therapeutic strategy for inducing vascular growth in the adult. As hMSCs are relatively easy to isolate from patients, and alginate is biocompatible and already used in clinical applications, therapeutic cell encapsulation for vascular repair represents a highly translatable platform for cell-based therapy in humans.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Landázuri
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Levit
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Giji
authors.initials: G
authors.lastname: Joseph
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Ortega-Legaspi
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Flores
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
authors.forename: Daiana
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.|School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Sambanis
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, USA.
authors.forename: Collin J
authors.initials: CJ
authors.lastname: Weber
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Safley
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA. wtaylor@emory.edu.|Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. wtaylor@emory.edu.|Cardiology Division, Atlanta Veterans Affairs Medical Center, Decatur, GA, USA. wtaylor@emory.edu.
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D002214:Capsules; D002470:Cell Survival / Q000187:drug effects; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019899:Paracrine Communication / Q000187:drug effects*; D010539:Permeability; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: cell therapy; experimental models; in vivo tracking; ischaemia; mesenchymal stem cells; paracrine; revascularization; tissue regeneration