School of Medicine and Health Sciences Poster Presentations

Title

Impact of Mesenchymal Stem/Stromal Cell Intra-arterial Delivery during Pediatric Cardiac Surgery on Neurogenesis in the Porcine Subventricular Zone

Document Type

Poster

Abstract Category

Cardiology/Cardiovascular Research

Keywords

Surgery, Cardiovascular, Neuroscience, Pediatrics

Publication Date

Spring 5-1-2019

Abstract

Introduction Congenital heart diseases is the leading birth defect, affecting almost 1% of births each year. Moreover, children who undergo cardiac surgery with cardiopulmonary bypass (CPB) show significant cognitive and behavioral impairments. The subventricular zone (SVZ) in the postnatal/adult brain is a very crucial region for neurogenesis and it plays an important role in neocortical growth of the gyrencephalic front lobe during postnatal life. Our preliminary data showed that CPB insults can cause a reduction in the neural stem progenitor cell (NSPC) pool. We have also observed a reduction in neurogenic activity and disruption in neuroblasts migration toward the frontal cortex. It has been shown that mesenchymal stem/stromal cell (MSC) promote neurogenesis form SVZ neural stem/progenitor cells on various rodent models. The aim of this study is to assess the short-term impact of MSC delivery through CPB on the NSPC pool in the SVZ of juvenile porcine model. Methods Two-week old piglets (n=12) were randomly assigned to one of 3 groups: (1) Control, (2) Deep hypothermic circulatory arrest (DHCA), and (3) DHCA followed by MSC administration. In the third group, MSCs (10x106 per kg) were delivered through CPB during the rewarming period. The piglet brains were fixed three hours after CPB. NSPCs and proliferation were determined by SOX2+ and Ki67+ antibodies. Neuroblasts and radial-glia like cells were identified by DCX+ and GFAP+ antibodies, respectively. The anterior-SVZ was dived into three tiers which were then subdivided into ventral and dorsolateral SVZ. Quantification of the NSPC and neuroblasts in each tier/region was performed, as these parameters reflect neurogenic activity. Results CPB insults increase the proliferative NSPCs three hours after surgery and this impact on proliferative NSPCs was confined to the dorsolateral-SVZ in the MSC group. Also, MSC delivery reduces the average length of the GFAP+ processes in the dorsolateral-SVZ while MSC delivery increases the density of DCX+ cells found in tiers 2 and 3. These findings may suggest that MSC delivery alters the distribution of neuroblasts. Conclusion Our data show that CPB insults cause proliferation of SVZ neural stem/progenitor cells. Moreover, our preliminary results suggest that MSC delivery has the potential to affect migratory stream of young neurons in SVZ in the acute phase. To determine the ameliorative effect of MSC delivery on neurogenesis, we will need to further investigate the SVZ in long term studies.

Open Access

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Presented at Research Days 2019.

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Impact of Mesenchymal Stem/Stromal Cell Intra-arterial Delivery during Pediatric Cardiac Surgery on Neurogenesis in the Porcine Subventricular Zone

Introduction Congenital heart diseases is the leading birth defect, affecting almost 1% of births each year. Moreover, children who undergo cardiac surgery with cardiopulmonary bypass (CPB) show significant cognitive and behavioral impairments. The subventricular zone (SVZ) in the postnatal/adult brain is a very crucial region for neurogenesis and it plays an important role in neocortical growth of the gyrencephalic front lobe during postnatal life. Our preliminary data showed that CPB insults can cause a reduction in the neural stem progenitor cell (NSPC) pool. We have also observed a reduction in neurogenic activity and disruption in neuroblasts migration toward the frontal cortex. It has been shown that mesenchymal stem/stromal cell (MSC) promote neurogenesis form SVZ neural stem/progenitor cells on various rodent models. The aim of this study is to assess the short-term impact of MSC delivery through CPB on the NSPC pool in the SVZ of juvenile porcine model. Methods Two-week old piglets (n=12) were randomly assigned to one of 3 groups: (1) Control, (2) Deep hypothermic circulatory arrest (DHCA), and (3) DHCA followed by MSC administration. In the third group, MSCs (10x106 per kg) were delivered through CPB during the rewarming period. The piglet brains were fixed three hours after CPB. NSPCs and proliferation were determined by SOX2+ and Ki67+ antibodies. Neuroblasts and radial-glia like cells were identified by DCX+ and GFAP+ antibodies, respectively. The anterior-SVZ was dived into three tiers which were then subdivided into ventral and dorsolateral SVZ. Quantification of the NSPC and neuroblasts in each tier/region was performed, as these parameters reflect neurogenic activity. Results CPB insults increase the proliferative NSPCs three hours after surgery and this impact on proliferative NSPCs was confined to the dorsolateral-SVZ in the MSC group. Also, MSC delivery reduces the average length of the GFAP+ processes in the dorsolateral-SVZ while MSC delivery increases the density of DCX+ cells found in tiers 2 and 3. These findings may suggest that MSC delivery alters the distribution of neuroblasts. Conclusion Our data show that CPB insults cause proliferation of SVZ neural stem/progenitor cells. Moreover, our preliminary results suggest that MSC delivery has the potential to affect migratory stream of young neurons in SVZ in the acute phase. To determine the ameliorative effect of MSC delivery on neurogenesis, we will need to further investigate the SVZ in long term studies.