Effect and mechanism of different ways of transplanting bone marrow mesenchymal stem cells in cardiopulmonary resuscitation in rats

Abstract

ABSTRACT. The effect and mechanism of different ways of transplanting bone marrow mesenchymal stem cells (MSCs) were explored for treating cardiopulmonary resuscitation in a rat model. Rats were divided into the cardiopulmonary resuscitation group (Group Con), the stereotactic lateral ventricle transplantation group (Group LV), the internal carotid artery transplantation group (Group A), and the femoral vein transplantation group (Group V). MSCs were transplanted in Groups LV, A, and V. The MSC transplantation groups had a significantly higher neurological score than Group Con on days 3 and 7 after recovery (P < 0.05), and the Group LV score was the highest in all groups (P < 0.05). On day 3 after recovery, the MSC count of Group LV was significantly higher than those of Groups A and V (P < 0.01). On day 7 after recovery, the MSC count in the hippocampus of Group LV was significantly higher than those of Groups A and V (P < 0.05). On day 3 after recovery, the S100B level of Group LV was significantly lower than those of Groups A and V (P < 0.05). On day 7 after recovery, the S100B level was not significantly different between the MSC transplantation groups (P > 0.05). The expressions of vascular endothelial growth factor and brain-derived neurotrophic factor did increased significantly in the MSC transplantation groups on day 7 after recovery, particularly Group LV. Therefore, MSC therapy could significantly improve nerve function after cardiopulmonary resuscitation, and stereotactic lateral ventricle injection transplantation is an optimal method.

Enhanced neuroprotective efficacy of bone marrow mesenchymal stem cells co-overexpressing BDNF and VEGF in a rat model of cardiac arrest-induced global cerebral ischemia

“…18, 19 Considering the advantage of neural stem cells for the treatment of brain damage, 20 we previously showed therapeutic benefits of transplantation of naive BMMSCs for suppressing CA-GCII in rats. 11, 21, 22 The observations from us as well as other groups suggest that increased expression of both BDNF and VEGF by the transplanted BMMSCs, at least in part, contribute to their neuroprotective activities. 11, 23 Furthermore, in our studies we found that, although direct lateral ventricular administration of BMMSCs provided highest efficiency to deliver the cells into the injured brain and to demonstrate the benefits, 11 the operational procedures were invasive and more complicated than the venous approach.…”

“…11, 21, 22 The observations from us as well as other groups suggest that increased expression of both BDNF and VEGF by the transplanted BMMSCs, at least in part, contribute to their neuroprotective activities. 11, 23 Furthermore, in our studies we found that, although direct lateral ventricular administration of BMMSCs provided highest efficiency to deliver the cells into the injured brain and to demonstrate the benefits, 11 the operational procedures were invasive and more complicated than the venous approach. Despite a high proportion of pulmonary retention, 24 certain number of BMMSCs administered intravenously still successfully migrated into lesioned zones of the brain with CA-GCII, particularly in the hippocampus and cortex.…”

“…These observations confirmed anchorage of the transplanted cells in these areas in the brain, which was consistent with our previous findings. 10, 11 Importantly, differential increases in the immunoreactivity of BDNF and VEGF were shown by immunohistochemistry in the same regions in the group transplanted with BDNF&VEGF-BMMSCs (i.e., BM-B&V) or naive BMMSCs (i.e., BM-Vehicle) in contrast to the group given PBS (Blank) or sham operated (Sham) (Figure 3), but the BM-B&V group demonstrated significantly more cells with higher intensity of immunostaining compared to all the other groups. Meanwhile, although the exactly same staining conditions were applied for all the brain sections, these from the BM-B&V group constantly exhibited higher background in both BDNF and VEGF staining than those from the other groups.…”

“…These results well reproduced our previous findings. 10, 11 Nevertheless, the nature of these cells needs to be further characterized, and studies are warranted to show whether engrafts have integrated into the neural network (Figure 3). Importantly, both immunohistochemistry and Western blotting analyses detected significantly increased expression of BDNF and VEGF in the brain with BM-B&V engraftment in contrast to all the other groups (Figure 3).…”

“…6, 7, 8, 9 We and others previously showed the therapeutic benefit of BMMSCs in CA-induced global cerebral ischemic injury (CA-GCII). 10, 11 Transplantation of BMMSCs significantly improved neural functional recovery of rats from CA-GCII. Mechanistic analysis suggests that the therapeutic efficacy of stem cells transplanted might be mediated by secreted vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF).…”