title: A combined cell therapy and in-situ tissue-engineering approach for myocardial repair.
abstract: Myocardial cell-replacement strategies are hampered by limited sources for human cardiomyocytes and by significant cell loss following transplantation. We tested the hypothesis that a combined delivery of cardiomyocytes with an in-situ polymerizable hydrogel into a post-MI rat heart will result in better functional outcomes than each intervention alone. A photopolymerizable, biodegradable, PEGylated-fibrinogen (PF) hydrogel matrix was used as the carrier for the cardiomyocytes [neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)]. Infarcted rat hearts (LAD ligation) were randomized to injection of saline, NRVCMs, biopolymer, or combined biopolymer-cell delivery. Echocardiography revealed typical post-infarction remodeling after 30 days in the saline-injected control group [deterioration of fractional shortening (FS) by 31.0 ± 3.6%]. Injection of NRVCMs or PF alone significantly (p < 0.01) altered this remodeling process (slightly increasing FS by 3.1 ± 6.6% and 0.5 ± 5.3% respectively). Co-injection of the NRVCMs with PF matrix resulted in a significant increase in the cell-graft area (by 144%) and in the highest improvements in FS (by 26.3 ± 6.6%). Finally, feasibility studies were performed with the PF matrix and hESC-CMs. We conclude that an injectable in-situ forming hydrogel can act as a cardiomyocyte cell-carrier and add to the beneficial effects of the grafted cells in preventing unfavorable post-infarction cardiac remodeling.
authors.affiliation: Bruce Rappaport Faculty of Medicine and Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Manhal
authors.initials: M
authors.lastname: Habib
authors.forename: Keren
authors.initials: K
authors.lastname: Shapira-Schweitzer
authors.forename: Oren
authors.initials: O
authors.lastname: Caspi
authors.forename: Amira
authors.initials: A
authors.lastname: Gepstein
authors.forename: Gil
authors.initials: G
authors.lastname: Arbel
authors.forename: Doron
authors.initials: D
authors.lastname: Aronson
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.forename: Lior
authors.initials: L
authors.lastname: Gepstein
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D004452:Echocardiography; D053595:Embryonic Stem Cells / Q000166:cytology; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D005340:Fibrinogen