Chemically induced decellularisation by Triton or Trypsine resulted in changes in the extracellular matrix constitution, which could lead to problems in valve functionality and cell growth and migration. Seeded endothelial cells were capable of synthesising extracellular matrix components lost by cell extraction. Further studies on tissue engineering should focus more on the effect of chemically induced cell extraction on the extracellular matrix of the remaining scaffold and the in vitro or in vivo replenishment of lost compounds.

Background-Proper development of compact myocardium, coronary vessels, and Purkinje fibers depends on the presence of epicardium-derived cells (EPDCs) in embryonic myocardium. We hypothesized that adult human EPDCs might partly reactivate their embryonic program when transplanted into ischemic myocardium and improve cardiac performance after myocardial infarction. Methods and Results-EPDCs were isolated from human adult atrial tissue. Myocardial infarction was created in immunodeficient mice, followed by intramyocardial injection of 4ϫ10 5 enhanced green fluorescent protein-labeled EPDCs (2-week survival, nϭ22; 6-week survival, nϭ15) or culture medium (nϭ24 and nϭ18, respectively). Left ventricular function was assessed with a 9.4T animal MRI unit. Ejection fraction was similar between groups on day 2 but was significantly higher in the EPDC-injected group at 2 weeks (short term), as well as after long-term survival at 6 weeks. End-systolic and end-diastolic volumes were significantly smaller in the EPDC-injected group than in the medium-injected group at all ages evaluated. At 2 weeks, vascularization was significantly increased in the EPDC-treated group, as was wall thickness, a development that might be explained by augmented DNA-damage repair activity in the infarcted area. Immunohistochemical analysis showed massive engraftment of injected EPDCs at 2 weeks, with expression of ␣-smooth muscle actin, von Willebrand factor, sarcoplasmic reticulum Ca 2ϩ -ATPase, and voltage-gated sodium channel (␣-subunit; SCN5a). EPDCs were negative for cardiomyocyte markers. At 6-weeks survival, wall thickness was still increased, but only a few EPDCs could be detected. Key Words: myocardial infarction Ⅲ stem cells Ⅲ remodeling Ⅲ magnetic resonance imaging Ⅲ angiogenesis C urrent therapy aimed at alleviating the sequelae of sustained myocardial infarction (MI) is not able to restore the function of the scarred area. Stem cell therapy poses a promising alternative therapy. Because therapeutic use of embryonic stem cells is an ethically intricate issue and is technically difficult in relation to the possible rejection of the cells and tumor formation, use of adult stem cells appears to be a more feasible option. Many different types of adult cells have been demonstrated to improve cardiac function after a MI, although the underlying mechanism has only been partially unraveled (for review, see Murry et al 1 ). Most of the cell types used are not known to be of importance during normal cardiogenesis. We chose to transplant epicardiumderived cells (EPDCs) because these cells are known to be crucial for cardiac development, because of both their physical contribution 2 and their modulatory role. 3,4 Conclusions-After Clinical Perspective p 927During embryogenesis, epicardium migrates from the extracardiac proepicardium to cover the premature heart, which by that time consists of only myocardium and endocardium, with cardiac jelly in between. 5 A subset of the epicardial cells undergoes epithelial-mesenchymal transformation (EMT...

Damage to the valves caused by decellularization technique is much less than the damage caused by the recipient's immune response. In vitro removal of viable cells in (cryopreserved) homografts may decrease graft failure. Seeding with autologous or major histocompatibility complex-matched donor endothelial cells will be necessary to diminish damage induced by an absent blood-tissue barrier.

Human mesenchymal stem cells (hMSCs) have only a limited differentiation potential toward cardiomyocytes. Forced expression of the cardiomyogenic transcription factor myocardin may stimulate hMSCs to acquire a cardiomyogenic phenotype, thereby improving their possible therapeutic potential. hMSCs were transduced with green fluorescent protein (GFP) and myocardin (hMSC myoc ) or GFP and empty vector (hMSC). After coronary ligation in immune-compromised NOD/scid mice, hMSC myoc (n ‫؍‬ 10), hMSC (n ‫؍‬ 10), or medium only (n ‫؍‬ 12) was injected into the infarct area. Sham-operated mice (n ‫؍‬ 12) were used to determine baseline characteristics. Left ventricular (LV) volumes and ejection fraction (EF) were serially (days 2 and 14) assessed using 9.4-T magnetic resonance imaging. LV pressure-volume measurements were performed at day 15, followed by histological evaluation. At day 2, no differences in infarct size, LV volumes, or EF were observed among the myocardial infarction groups. At day 14, left ventricular ejection fraction in both cell-treated groups was preserved compared with the nontreated group; in addition, hMSC myoc injection also reduced LV volumes compared with medium injection (p < .05). Furthermore, pressure-volume measurements revealed a significantly better LV function after hMSC myoc injection compared with hMSC treatment. Immunohistochemistry at day 15 demonstrated that the engraftment rate was higher in the hMSC myoc group compared with the hMSC group (p < .05). Furthermore, these cells expressed a number of cardiomyocyte-specific markers not observed in the hMSC group. After myocardial infarction, injection of hMSC myoc improved LV function and limited LV remodeling, effects not observed after injection of hMSC. Furthermore, forced myocardin expression improved engraftment and induced a cardiomyocyte-like phenotype hMSC differentiation.