Priya Reddy

School: The Ohio State University

Major: Neuroscience

DOI: https://doi.org/10.21985/n2-8wwq-k939

Biography:

Priya is a junior at The Ohio State University majoring in neuroscience with a minor in disability studies. She is a part of Dr. Mestan’s lab and investigates the effect of cord blood-derived monocytes on fetal lungs. Priya plans to pursue an MD after graduation. In her free time, she enjoys dancing, volunteering at her local food pantry, and playing tennis.

Hyperoxia-Induced Lung Engraftment of Human Cord Blood Monocytes in a Humanized Mouse Model of Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is often characterized by chronic lung injury secondary to high levels of oxygen during the neonatal period. Previous studies have demonstrated that administration of human cord blood (CB) monocytes results in decreased alveolar damage due to hyperoxia exposure but fail to demonstrate engraftment of these cells in the lungs of the animal model. We hypothesize that administration of human CB monocytes in MISTRG humanized mice ameliorate the BPD-like phenotype after hyperoxia exposure. Cord blood was collected after delivery and processed within 36 hours. Monocytes and CD34+ cells were isolated by magnetic-activated cell sorting and intra-hepatically injected at Day 0-1 of life. Pups were then exposed to normoxia (21% oxygen) or hyperoxia (85%) for 7 days. Lungs and livers were harvested, and H&E staining and immunohistochemistry for human CD45 were performed. Alveolar count and area were measured and CD45 expression was quantified. Immunohistochemistry confirmed human CD45 expression in the liver and lung after intra-hepatic injection of CB cells. The presence of human CD45+ cells in the liver was more pronounced with CB monocytes versus CD34+ cells and in mice exposed to hyperoxia versus normoxia (P<0.01). Engraftment of CD45 cells was demonstrated in the lungs of mice injected with both monocytes and CD34+ cells, and in mice injected with sorted monocytes, but not in mice treated with isolated CD34+ cells. Preliminarily, CD45 positively-stained cells appeared more prominent with hyperoxia exposure, and lung histology revealed a trend towards increased alveolar number and decreased alveolar area in mice injected with sorted CB monocytes. These associations indicate that intra-hepatic delivery of CB-derived monocytes leads to engraftment of human CD45+ cells in murine lungs and attenuates alveolar simplification due to hyperoxia. Completion of the above studies will demonstrate the extent to which CB monocytes may have a protective effect on neonatal lungs exposed to hyperoxia.

Author Q&A

What is your research topic, in a nutshell?

My research looks into the therapeutic effects of human cord blood monocytes on fetal lung injury. Specifically, it is focused on demonstrating engraftment of these cells in the lungs of a MISTRG mouse model of Bronchopulmonary Dysplasia (BPD) while also confirming that administration of these monocytes ameliorates the BPD-like phenotype after exposure to hyperoxia. 

How did you come to your research topic? 

Previous studies have demonstrated that administration of human cord blood monocytes results in decreased alveolar damage due to hyperoxia exposure but they have failed to demonstrate engraftment of these cells in the lungs. This has led us to focus on demonstrating cell engraftment in the lungs. In general, my lab is focused on the management and prevention of neonatal chronic lung diseases. This focus has greatly influenced my research topic. 

Where do you see the future direction of this work leading (how might future researchers build on your work or what is left to discover in this field)? 

Some next steps of this work include looking into the influence of clinical characteristics of the patients (IUGR, chorioamnionitis, placental insufficiency) from which MNCs are derived on engraftment and alveolar histology. In addition, future researchers can see if different MNC subsets (classical, intermediate, and non-classical) have different effects on engraftment and alveolar histology. Lastly, the interaction of intrauterine growth restriction (Thromboxane A2 analog) and hyperoxia on MNC engraftment can be studied.

Where are you heading to after graduation?  

I plan to attend medical school after graduation!