Effects of endothelial and mesenchymal stem cells on improving myocardial function in a sheep animal model

Background: myocardial infarction is the main cause of death worldwide. Angiogenesis, a promising new therapy for the treatment of diffuse coronary artery disease, shows a poor response to conventional revascularization techniques. This study focused on improving myocardial function using endothelial cells [ECs] and mesenchymal stem cells [MSCs] in a sheep animal model

Methods: acute myocardial infarction was induced in 18 sheep [12 treated cases and 6 controls]. Autologous MSCs and ECs were injected in the infarcted area and the border zone. Two months after transplantation, echocardiography, electron microscopy, and immunohistochemistry were performed

Results: echocardiography in both MSC and EC groups revealed a significant improvement in the ejection fraction compared with the control group [p value < 0.05]. Vascular density, estimated by antibodies against the von Willebrand factor and smooth muscle actin, increased in both study groups. The pattern of vascularity in the MSC and EC groups was diffused. The electron microscopic evaluation of the infracted areas revealed cardiomyocytes in variable stages of development in the border zone in both EC and MSC groups

Conclusion: both ECs and MSCs were able to promote angiogenesis and improve cardiac function. Presumably, MSCs differentiate into ECs and cause angiogenesis as it occurs for ECs

Effect of supplementary zinc on orthodontic tooth movement in a rat model

ABSTRACT Introduction: Osteoclasts and osteoblasts are responsible for regulating bone homeostasis during which the trace element zinc has been shown to exert a cumulative effect on bone mass by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. Objective: The aim of the present study was to investigate the effects of zinc (Zn) on orthodontic tooth movement (OTM) in a rat model. Material and Methods: A total of 44 male Wistar rats were divided into four groups of 11 animals each and received 0, 1.5, 20 and 50 ppm Zn in distilled water for 60 days. In the last 21 days of the study, nickel-titanium closed coil springs were ligated between maxillary right incisors and first molars of all rats, and tooth movement was measured at the end of this period. Histological analysis of hematoxylin/eosin slides was performed to assess root resorption lacunae, osteoclast number and periodontal ligament (PDL) width. Results: Mean OTM was calculated as 51.8, 49.1, 35.5 and 45 µm in the 0, 1.5, 20 and 50 ppm zinc-receiving groups, respectively. There were no significant differences in neither OTM nor histological parameters among the study groups (p > 0.05). Conclusion: According to the results obtained in the current investigation, increase in supplementary zinc up to 50 ppm does not affect the rate of OTM neither bone and root resorption in rats.

RESUMO Introdução: os osteoclastos e os osteoblastos são responsáveis por regular a homeostase óssea, processo no qual o oligoelemento zinco tem demonstrado exercer um efeito cumulativo sobre a massa óssea, estimulando a formação óssea osteoblástica e inibindo a reabsorção óssea osteoclástica. Objetivo: o objetivo do presente estudo foi investigar os efeitos do zinco (Zn) sobre a movimentação dentária ortodôntica (MDO) em ratos. Métodos: um total de 44 ratos Wistar machos foi dividido em quatro grupos de 11 animais cada, os quais receberam 0; 1,5; 20 e 50ppm de zinco diluído em água destilada, durante 60 dias. Nos últimos 21 dias do estudo, molas helicoidais fechadas de níquel-titânio foram instaladas entre os incisivos direitos e os primeiros molares superiores de todos os ratos, e a movimentação dentária foi medida ao final desse período. Foi realizada análise histológica de cortes corados por hematoxilina-eosina, para avaliar as lacunas de reabsorção radicular, o número de osteoclastos e a espessura do ligamento periodontal. Resultados: as médias da MDO foram estimadas em 51,8; 49,1; 35,5 e 45µm no grupos que receberam, respectivamente, 0; 1,5; 20 e 50ppm de zinco. Não houve diferença significativa entre os grupos experimentais, nem quanto à MDO, nem quanto aos parâmetros histológicos (p > 0,05). Conclusão: segundo os resultados obtidos na presente investigação, verificou-se que um aumento na dose de suplementação com zinco para 50ppm não afeta nem o índice de MDO, nem a reabsorção óssea ou radicular em ratos.

comparative study of recombinant human basic fibroblast growth factor [bFGF] and erythropoietin [EPO] in prevention of skin flap ischemic necrosis in rats

Impaired wound healing in ischemic tissues such as skin flaps resulting from inefficient perfusion is one major cause of complications in plastic surgery. In present experimental study, we investigated the effects of fibroblast growth factor-2 [FGF-2 or bFGF] and erythropoietin [EPO] in prevention of skin flap necrosis in rats. 30 adult albino rats were randomized into 3 groups: in control group, normal saline solution; in EPO group, erythropoietin [100U/ kg/day]: and in FGF-2 group, fibroblast growth factor-2 [2,5 microg/day] were injected subcutaneously in 3 daily consecutive doses in the designated flap areas before creating 4:1 random pattern skin flaps on the dorsum of animals. Areas of ischemic [S] and necrotic [S[N]] zones were measured and compared in all groups one week after the flap creations. The necrotic zone [S[N]], as well as the ratio of the necrotic zone to the total discolored zone [S[N]/[S[I]+S[N]]] were substantially larger in the control group [41% +/- 7%, 90% +/- 6%] compared to the EPO [20% +/- 2%,42% +/- 4%] and the FGF-2 [8% +/- 2%,19% +/- 3%] groups [p < 0.001]. The differences in these values were also meaningful between the EPO and FGF-2 groups [p < 0.001].Vascular density in ischemic area of the control group was less than those in the EPO and the FGF-2 groups; however, the differences were not statistically significant between any of the groups [p > 0.05]. Local administration of erythropoietin or fibroblast growth factor-2 in skin flaps could remarkably increase tissue viability and accelerate the wound healing process. However, the therapeutic effect of fibroblast growth factor-2 in preventing the necrotic event in, ischemic zones of skin flaps is much more considerable than that of erythropoietin

Comparison between transepicardial cell transplantations: Autologus undifferentiated versus differentiated marrow mesenchymal stem cells

Marrow-derived mesenchymal stem cells [MSCs] have been heralded as a source of great promise for the regeneration of the infarcted heart. There are no clear data as to whether or not in vitro differentiation of MSCs into major myocardial cells can increase the beneficial effects of MSCs. The aim of this study was to address this issue. To induce MSCs to transdifferentiate into cardiomyocytes and endothelial cells, 5-Azacytidine and vascular endothelial growth factor [VEGF] were used, respectively. Myocardial infarction in rabbits was generated by ligating the left anterior descending coronary artery. The animals were divided into three experimental groups: I] control group, II] undifferentiated mesenchymal stem cell transplantation group, and III] differentiated mesenchymal stem cell transplantation group. The three groups received peri-infarct injections of culture media, autologous undifferentiated MSCs, and autologous differentiated MSCs, respectively. Echocardiography and pathology were performed in order to search for improvement in the cardiac function and reduction in the infarct size. Improvements in the left ventricular function and reductions in the infarcted area were observed in both cell transplanted groups [Groups II and III] to the same degree. There is no need for prior differentiation induction of marrow-derived MSCs before transplantation, and peri-infarct implantation of MSCs can effectively reduce the size of the infarct and improve the cardiac function

Induced Myocardial Infarction Using Ligation of the Left Anterior Descending Coronary Artery Major Diagonal Branch: Development of an Ovine Model

We report experimental myocardial infarction by occluding coronary arteries in ovine models. Twelve ewes were included in the study. After the chest was opened by left lateral thoracotomy incision, the second diagonal branch of the left anterior descending coronary artery was ligated at a point approximately 40% distant from its base. Prophylactic antiarrhythmics were administered. Animals were mechanically ventilated during surgery and stayed in the ICU for 24h afterwards. Experiments were then evaluated by echocardiographic, electrocardiographic, hemodynamic, serologic and morphologic investigations. Echocardiographic measurements were repeated after two months and animals were then sacrificed for postmortem cardiac examinations. All animals survived the surgical procedure. Cyanotic discoloration and hypokinesia in the cardiac tissue in an area of 3x4 cm plus ST-segment elevations was detected immediately after vessel ligation. More over, there were pathologic Q-waves 2 months later. Echocardiographic evaluations revealed an average of 22% relative decrease in cardiac ejection fraction. Wall motion analysis demonstrated anteroapical hypokinesia and akinesia in all animals one day and two months after operation. Thin walled infarcted areas with tissue fibrosis were evident in pathologic investigations two months after surgery. In conclusion, we developed a practical and safe method of producing myocardial infarction in large animal models