700 - Biologic Potential of Human Preterm Umbilical Cord Derived Mesenchymal Stem Cells Exposed to Maternal Marijuana and Active SARS-CoV-2 Infection at Delivery

Saturday, April 29, 2023

3:30 PM – 6:00 PM ET

Poster Number: 700
Publication Number: 700.233

Adnan Ismail, UC Irvine & CHOC Children's Hospital of Orange County, Orange, CA, United States; Fayez Bany-Mohammed, University of California, Irvine, School of Medicine, Orange, CA, United States; Cherry Uy, University of California, Irvine, School of Medicine, Orange, CA, United States; Muhammad Aslam, University of California, Irvine, School of Medicine, Orange, CA, United States

Presenting Author(s)

AI

Adnan Ismail, MD (he/him/his)

Neonatologist
UC Irvine & CHOC Children's Hospital of Orange County
Orange, California, United States

Background: COVID-19 caused by the SARS-CoV-2 virus has led to a pandemic with oxidative stress, inflammatory cascade, and cytokine storm as main causes of morbidity and mortality. Pregnant women are at higher risk of viral infections given an alteration in immune response. The infection in pregnant women varies from asymptomatic to severe disease depending on the degree of inflammation and cytokine storm. At present, limited data are available to show the effects of maternal marijuana use and Covid infection on the biologic efficacy of umbilical cord derived mesenchymal stem cells (MSCs).

Objective:

To determine the biologic potential of human preterm MSCs expsoded to marijuana and Covid-19 at delivery.

Design/Methods:

The umbilical cords at preterm delivery (24-28 weeks’ gestational age) were collected from four groups (n=6/group) as follows:

Group A: Normal (no marijuana use with negative SARS-CoV-2 infection)

Group B: Non-Covid Marijuana (Marijuana use with negative SARS-CoV-2 infection)

Group C: Covid Marijuana (marijuana use with positive SARS-CoV-2 infection)

Group D: Covid Non-Marijuana (no marijuana use with positive SARS-CoV-2 infection).

Marijuana use determined by positive maternal urine THC at delivery. Covid status determined by SARS-CoV-2 PCR at delivery. The umbilical cord Wharton’s jelly plastic adherent cells harvested, propagated, and immunodepleted to obtain MSCs. MSC duplication and differentiation time assessed between four groups. MSC-CM generated and proteomics analysis done to determine secreted biomarkers. Endogenous MSC mitochondrial bioenergetics, proliferation, and survival analysis assessed using commercial kits and published protocols.

Results:

Group C (Marijuana and Covid positive) showed a much shorter duplication time and differentiation time (adipocytes and osteocytes) when compared with other groups. Proteomics analysis identified significantly lower lung injury preventive biomarkers concentration in Group C MSC-CM compared to other groups MSC-CM. Group C MSCs showed mitochondrial dysfunction with increased oxidative stress when compared with other groups MSCs. Hyperoxia-exposed Group C MSCs showed decreased mitophagy compared to other group control MSCs. Apoptosis assay showed significantly more apoptosis in Group C MSCs compared to other groups MSCs. All these results were statistically significant.

Conclusion(s):

Maternal marijuana use and active SARS-CoV-2 infection at the time of delivery alters the biologic potential of human preterm umbilical cord derived MSCs with lack of protected biomarkers and increased oxidative stress with mitochondrial dysfunction.