Formation of Nascent Intercalated Disks Between Grafted Fetal Cardiomyocytes and Host Myocardium

Abstract

Fetal cardiomyocytes isolated from transgenic mice carrying a fusion gene of the alpha-cardiac myosin heavy chain promoter with a beta-galactosidase reporter were examined for their ability to form stable intracardiac grafts. Embryonic day 15 transgenic cardiomyocytes delivered directly into the myocardium of syngeneic hosts formed stable grafts, as identified by nuclear beta-galactosidase activity. Grafted cardiomyocytes were observed as long as 2 months after implantation, the latest date assayed. Intracardiac graft formation did not induce overtly negative effects on the host myocardium and was not associated with chronic immune rejection. Electron microscopy revealed the presence of nascent intercalated disks connecting the engrafted fetal cardiomyocytes and the host myocardium. These results suggest that intracardiac grafting might provide a useful approach for myocardial repair, provided that the grafted cells can contribute to myocardial function.

Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: Diagnosis and management

“…Novel surgical therapies include left ventricular remodelling, mechanical circulatory assistance and, more recently, isolated cell transplantation or gene therapy (111)(112)(113)(114)(115)(116). The advent of cell transplantation provides great promise for the future because it may be a useful adjunct to several of the previously mentioned therapies.…”

β-Galactosidase staining following intracoronary infusion of cationic liposomes in the in vivo rabbit heart is produced by microinfarction rather than effective gene transfer: a cautionary tale

“…[1][2][3] Successful gene expression has followed direct intramyocardial injection, [4][5][6][7][8][9][10][11] the introduction into the myocardium of cells transfected ex vivo, [12][13][14] pericardial gene transfer, 15 intracoronary dwell in the arrested heart, [16][17][18][19] and percutaneous transarterial coronary infusion (PTCI). 8,[20][21][22][23] Most investigators have concentrated on the feasibility and characterisation of in vivo myocardial gene transfer and therefore used biologically inert reporter genes.…”

Tissue engineering in the cardiovascular system: Progress toward a tissue engineered heart

“…These cells survived and formed new tissue that resembled cardiac muscle at the site of injury. Similar studies have been performed by using embryonic cardiac myocytes (Soonpaa et al, 1994), myoblast cell lines (Koh et al, 1993), and cardiomyocytes, smooth muscle cells, and fibroblasts seeded onto scaffolds (Li et al, 1999(Li et al, , 2000Carrier et al, 1999). Carrier et al (1999) have also begun to look at the influence of seeding conditions and different bioreactors when culturing seeded scaffolds.…”