Mesenchymal stem cells (MSCs) are a cell population present in adult tissues that can be isolated and culturable in vitro. It has been reported that MSCs can differentiate in many cell types, including cartilage, bone, tendon, ligaments, muscles, skin and even nerve cells. Since they are autologous and do not raise immunological and ethical problems, MSCs are attracting the attention by scientific community. MSCs are usually obtained from bone marrow, peripheral blood, cord blood, muscle, brain, adipose tissue, skin or gut. Several studies reported a clinical benefit by bone marrow or adipose tissue MSCs injection after myocardial infarction and other heart diseases. However, few data are reported about early homing of these cells in damaged organs. All these considerations moved us to assess activity of our MSCs obtained from adult teeth dental pulp (MSCDPs) in an infarcted heart model. We first characterized MSCDPs in vitro, then we studied the homing behaviour in an ex vivo model of infracted heart. Our characterization study demonstrated that they are multipotent cells with excellent differentiation potentiality. In vitro experiments showed that after adequate stimuli, they can differentiate into precursor of many different cell types such as adipocytes, chondrocytes, osteocytes, nervous system cells and cardiomyocytes. These features are likely due to their precocious isolation from surrounding tissues during embryogenesis (i.e. during the formation of the dental papilla). For the ex vivo studies, we used isolated rat hearts perfused according to Langendorff’s model. Specifically, we considered the homing of MSCDPs injected in apical zone of both normal and infarcted hearts, over the first 4 hours after inoculation. Ischemic injuries were performed by means of anterior descendent coronary artery ligation for 30 minutes. Five minutes after the release of coronary occlusion, 106 MSCDPs were injected into the left ventricle apex. In order to evaluate the location and extension of injured area, after 4 hours reperfusion (i.e. at the end of the experiment), hearts were perfused with trypan blue, a specific damaged cells dye. Intriguingly, we observed that MSCDPs remain in the site of injection forming round-shaped cells clusters in normal hearts, while in infarcted ones MSCDPs migrate very early towards the injured areas, as evidenced by trypan blue stain. Yet they start to elongate side by side with cardiomyocytes. In conclusion, MSCDPs isolated from dental pulp could provide an excellent model for development of stem cell therapies. Moreover our data suggest that they can integrate within the myocardium. Future studies can ascertain the potential applications of MSCDPs in repairing injured hearts and in improving their function.
Dental pulp derived mesenchymal stem cells in myocardial infarction experimental models: preliminary results
DI SCIPIO, FEDERICA;SPRIO, ANDREA ELIO;FOLINO, Anna;SALAMONE, PAOLINA;RASTALDO, Raffaella;PAGLIARO, Pasquale;DI CARLO, Francesco;BERTA, Giovanni Nicolao
2009-01-01
Abstract
Mesenchymal stem cells (MSCs) are a cell population present in adult tissues that can be isolated and culturable in vitro. It has been reported that MSCs can differentiate in many cell types, including cartilage, bone, tendon, ligaments, muscles, skin and even nerve cells. Since they are autologous and do not raise immunological and ethical problems, MSCs are attracting the attention by scientific community. MSCs are usually obtained from bone marrow, peripheral blood, cord blood, muscle, brain, adipose tissue, skin or gut. Several studies reported a clinical benefit by bone marrow or adipose tissue MSCs injection after myocardial infarction and other heart diseases. However, few data are reported about early homing of these cells in damaged organs. All these considerations moved us to assess activity of our MSCs obtained from adult teeth dental pulp (MSCDPs) in an infarcted heart model. We first characterized MSCDPs in vitro, then we studied the homing behaviour in an ex vivo model of infracted heart. Our characterization study demonstrated that they are multipotent cells with excellent differentiation potentiality. In vitro experiments showed that after adequate stimuli, they can differentiate into precursor of many different cell types such as adipocytes, chondrocytes, osteocytes, nervous system cells and cardiomyocytes. These features are likely due to their precocious isolation from surrounding tissues during embryogenesis (i.e. during the formation of the dental papilla). For the ex vivo studies, we used isolated rat hearts perfused according to Langendorff’s model. Specifically, we considered the homing of MSCDPs injected in apical zone of both normal and infarcted hearts, over the first 4 hours after inoculation. Ischemic injuries were performed by means of anterior descendent coronary artery ligation for 30 minutes. Five minutes after the release of coronary occlusion, 106 MSCDPs were injected into the left ventricle apex. In order to evaluate the location and extension of injured area, after 4 hours reperfusion (i.e. at the end of the experiment), hearts were perfused with trypan blue, a specific damaged cells dye. Intriguingly, we observed that MSCDPs remain in the site of injection forming round-shaped cells clusters in normal hearts, while in infarcted ones MSCDPs migrate very early towards the injured areas, as evidenced by trypan blue stain. Yet they start to elongate side by side with cardiomyocytes. In conclusion, MSCDPs isolated from dental pulp could provide an excellent model for development of stem cell therapies. Moreover our data suggest that they can integrate within the myocardium. Future studies can ascertain the potential applications of MSCDPs in repairing injured hearts and in improving their function.
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