title: Naive rat amnion-derived cell transplantation improved left ventricular function and reduced myocardial scar of postinfarcted heart.
abstract: Stem cells contained in the amniotic membrane may be useful for cellular repair of the damaged heart. Previously, we showed that amnion-derived cells (ADCs) express embryonic stem cell surface markers and pluripotent stem cell-specific transcription factor genes. These ADCs also possess the potential for mesoderm (cardiac) lineage differentiation. In the present study we investigated whether untreated naive ADC transplantation into the injured left ventricular (LV) myocardium is beneficial as a cell-based cardiac repair strategy in a rat model. ADCs were isolated from Lewis rat embryonic day 14 amniotic membranes. FACS analysis revealed that freshly isolated ADCs contained stage-specific embryonic antigen-1 (SSEA-1), Oct-4-positive cells, and mesenchymal stromal cells, while hematopoietic stem cell marker positive cells were absent. Reverse transcription-PCR revealed that naive ADCs expressed cardiac and vascular specific genes. We injected freshly isolated ADCs (2 x 10(6) cells suspended in PBS, ADC group) into acutely infarcted LV myocardium produced by proximal left coronary ligation. PBS was injected in postinfarction controls (PBS group). Cardiac function was assessed at 2 and 6 weeks after injection. ADC treatment attenuated LV dilatation and sustained LV contractile function at 2 and 6 weeks in comparison to PBS controls (p < 0.05, ANOVA). LV peak systolic pressure and maximum dP/dt of ADC-treated heart were higher and LV end-diastolic pressure and negative dP/dt were lower than in PBS controls (p < 0.05). Histological assessment revealed that infarcted myocardium of the ADC-treated group had less fibrosis, thicker ventricular walls, and increased capillary density (p < 0.05). The fate of injected ADCs was confirmed using ADCs derived from EGFP(+) transgenic rats. Immunohistochemistry at 6 weeks revealed that EGFP(+) cells colocalized with von Willebrand factor, alpha-smooth muscle actin, or cardiac troponin-I. Our results suggest that naive ADCs are a potential cell source for cellular cardiomyoplasty.
authors.affiliation: Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kazuro L
authors.initials: KL
authors.lastname: Fujimoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Miki
authors.forename: Li J
authors.initials: LJ
authors.lastname: Liu
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Hashizume
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Strom
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D016277:Ventricular Function, Left
chemical_list: D000943:Antigens, Differentiation