title: Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium.
abstract: The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly in vivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy.
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Blocki
authors.affiliation: Singapore MIT Alliance for Research and Technology (SMART), BioSyM Interdisciplinary Research Group, Singapore.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beyer
authors.affiliation: NUS Graduate School for Engineering and Integrative Sciences (NGS), National University of Singapore, Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore; NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Dewavrin
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore; NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Goralczyk
authors.affiliation: NUS Graduate School for Engineering and Integrative Sciences (NGS), National University of Singapore, Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore; NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Yingting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore; NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Peh
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Ng
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Shehzahdi S
authors.initials: SS
authors.lastname: Moonshi
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Susmitha
authors.initials: S
authors.lastname: Vuddagiri
authors.affiliation: NUS Graduate School for Engineering and Integrative Sciences (NGS), National University of Singapore, Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore; NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Raghunath
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Eliana C
authors.initials: EC
authors.lastname: Martinez
authors.affiliation: Singapore Bioimaging Consortium (SBIC), Biomedical Sciences Institute, Agency for Science, Technology and Research (A*STAR), Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: Kishore_Bhakoo@sbic.a-star.edu.sg.
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Bhakoo
mesh_terms: D000818:Animals; D002214:Capsules; D049109:Cell Proliferation; D002470:Cell Survival; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009203:Myocardial Infarction / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002214:Capsules
keywords: Biocompatibility; Cell encapsulation; Cell therapy; Foreign body response; In vivo cell tracking; Myocardial infarction