Background-Autologous bone marrow cells (BMCs) transplanted into ventricular scar tissue may differentiate into cardiomyocytes and restore myocardial function. This study evaluated cardiomyogenic differentiation of BMCs, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function. Methods and Results-In vitro studies: BMCs from adult rats were cultured in cell culture medium (control) and medium with 5-azacytidine (5-aza, 10 mol/L), TGF␤1 (10ng/mL), or insulin (1 nmol/L) (nϭ6, each group). Only BMCs cultured with 5-aza formed myotubules which stained positively for troponin I and myosin heavy chain. In vivo studies: a cryoinjury-derived scar was formed in the left ventricular free wall. At 3 weeks after injury, fresh BMCs (nϭ9), cultured BMCs (nϭ9), 5-aza-induced BMCs (nϭ12), and medium (control, nϭ12) were autologously transplanted into the scar. Heart function was measured at 8 weeks after myocardial injury. Cardiac-like muscle cells which stained positively for myosin heavy chain and troponin I were observed in the scar tissue of the 3 groups of BMC transplanted hearts. Only the 5-aza-treated BMC transplanted hearts had systolic and developed pressures which were higher (PϽ0.05) than that of the control hearts. All transplanted BMCs induced angiogenesis in the scar. Conclusions-Transplantation of BMCs induced angiogenesis. BMCs cultured with 5-aza differentiated into cardiac-like muscle cells in culture and in vivo in ventricular scar tissue and improved myocardial function. (Circulation. 1999;100[suppl II]:II-247-II-256.

Development of AKI within the first 72 h after transplant impacted short-term and long-term graft survival.

The greatest part of liver allograft injury occurs during reperfusion, not during the cold ischemia phase. The aim of this study, therefore, was to investigate how the severity of postreperfusion syndrome (PRS) influences short-term outcome for the patient and for the liver allograft. Over a 2-year period, 338 consecutive patients who presented for orthotopic liver transplantation (OLT) were included in this retrospective study. They were divided into 2 groups according to the severity of the PRS they experienced. The first group comprised 152 patients with mild or no PRS; the second group comprised 186 patients with significant PRS. Perioperative hemodynamic parameters, coagulation profiles, blood product requirements, incidence of infection, incidence of rejection and outcome data for both groups were collected and analyzed. There was no demographic difference between the groups except for age; group 2 had older patients than group 1 (54.94 Ϯ 9.07 versus 51.52 Ϯ 9.91, P ϭ 0.001). Compared to group 1, group 2 patients required more red blood cell transfusions (11.31 Ϯ 10.90 versus 8.08 Ϯ 7.89 units, P ϭ 0.002), more fresh frozen plasma transfusions (10.25 Ϯ 10.96 versus 7.03 Ϯ 7.64 units, P ϭ 0.002), more cryoprecipitate (1.88 Ϯ 4.72 units versus 0.61 Ϯ 1.80 units, P ϭ 0.001), and were more likely to suffer from fibrinolysis (52.7% versus 41.4%, P ϭ 0.041). Interestingly, group 2 had a shorter average warm ischemia time than group 1 (33.19 Ϯ 8.55 versus 36.21 Ϯ 11.83 minutes, P ϭ 0.01). Group 2 also required longer, on average, mechanical ventilation (14.95 Ϯ 29.79 versus 8.55 Ϯ 17.79 days, P ϭ 0.015), remained in the intensive care unit longer (17.65 Ϯ 31.00 versus 11.49 Ϯ 18.67 days, P ϭ 0.025), and had a longer hospital stay (27.29 Ϯ 32.35 versus 20.85 Ϯ 21.08 days, P ϭ 0.029). Group 2 was more likely to require retransplantation (8.6% versus 3.3%, P ϭ 0.044). In conclusion, the severity of PRS during OLT appears to be related to the outcome of patient and liver allograft.

Myoblast transplantation for cardiac repair has generated beneficial results in both animals and humans; however, poor viability and poor engraftment of myoblasts after implantation in vivo limit their regeneration capacity. We and others have identified and isolated a subpopulation of skeletal muscle-derived stem cells (MDSCs) that regenerate skeletal muscle more effectively than myoblasts. Here we report that in comparison with a myoblast population, MDSCs implanted into infarcted hearts displayed greater and more persistent engraftment, induced more neoangiogenesis through graft expression of vascular endothelial growth factor, prevented cardiac remodeling, and elicited significant improvements in cardiac function. MDSCs also exhibited a greater ability to resist oxidative stress-induced apoptosis compared to myoblasts, which may partially explain the improved engraftment of MDSCs. These findings indicate that MDSCs constitute an alternative to other myogenic cells for use in cardiac repair applications.