Cardiomyocyte Transplantation in a Porcine Myocardial Infarction Model

Abstract

Transplantation of cardiomyocytes into the heart is a potential treatment for replacing damaged cardiac muscle. To investigate the feasibility and efficiency of this technique, either a cardiac-derived cell line (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were grafted into a porcine model of myocardial infarction. The myocardial infarction was created by the placement of an embolization coil in the distal portion of the left anterior descending artery in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three preparations of cardiomyocytes were grafted, at 1 x 10(6) cells/20 microL into normal and into the middle of the infarcted myocardium. The hearts were harvested and processed for histologic examinations 4 to 5 wk after the cell grafts. Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal pig cardiomyocytes formed stable grafts within the normal myocardium without any detrimental effect including arrhythmia. In addition, a marked increase in angiogenesis was observed both within the grafts and adjacent host myocardium. Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the host myocardial cells were coupled with adherens-type junctions and gap junctions. Histologic examination of graft sites from infarct tissue failed to show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes. Cardiomyocyte transplantation may provide the potential means for cell-mediated gene therapy for introduction of therapeutic molecules into the heart.

Reactive Oxygen Species Inhibit Adhesion of Mesenchymal Stem Cells Implanted into Ischemic Myocardium via Interference of Focal Adhesion Complex

“…Autologous MSCs offer a great advantage when used to generate functional cardiac myocytes because they can be easily prepared from adult patients and they are immunologically safe. However, the frequency of MSC engraftment is extremely low despite the implantation of large numbers of cells due to a low rate of cell adhesion and survival [24]. Despite the numerous approaches that have been attempted to overcome these limitations and dramatically improve cardiac function in a rodent MI model, there is still no solution to the problem of anoikis, programmed cell death induced by loss of matrix attachments [8].…”

Regulation of cardiomyocyte maturation during critical perinatal window

“…For example, some studies have observed significant and near-complete maturation of transplanted cells by structural and electrophysiological analysis, including primary cells (Klug et al 1996;Gojo et al 1997;Roell et al 2002;Rubart et al 2003) and PSC-CMs (Didié et al 2013). On the other hand, other studies have shown only partial and limited maturation even following extended transplantation, with failure to achieve full adult size and structure (Leor et al 1996;Watanabe et al 1998;Reinecke et al 1999;Müller-Ehmsen et al 2002;Christoforou et al 2010;Shiba et al 2016). Likewise, we have observed that transplantation of ESC-CMs at p14 resulted in limited maturation with incomplete sarcomere alignment .…”

Cardiac stem cells

“…CCM can be used to ameliorate the remodelling process by the regeneration of cardiomyocytes and replenishment of the vascular supply. Historically, a wide range of cell types has been used for CCM, including embryonic, fetal, and neonatal rodent and porcine cardiomyocytes5–11; fetal smooth muscle cells12; AT‐1 tumour cardiomyocytes13 and human adult and fetal cardiomyocytes6, 14, 15; autologous adult atrial cells16; and dermal fibroblasts17. Irrespective of cell type, the enhanced myocardial performance which accompanies CCM is attributable to a combination of factors.…”