325 - Therapeutic Potential of Human Preterm Umbilical Cord Derived Mesenchymal Stem Cell Exosomes Exposed to Maternal Marijuana at Delivery in Experimental Bronchopulmonary Dysplasia

Publication Number: 325.6825

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

Background: Human umbilical cord mesenchymal stem cells (MSCs) have shown promising results in murine experimental BPD. Maternal antenatal drugs and disease states can affect the efficacy of MSCs. At present, very limited data are available on maternal marijuana use during pregnancy affecting the MSC biologic potential. This study evaluated therapeutic potential of MSC-exo harvested from umbilical cords of preterm infants with and without marijuana exposure at delivery in murine BPD.

Objective: We hypothesized that maternal marijuana use at the time of preterm delivery will lead to a decline in therapeutic efficacy of preterm umbilical cord derived MSC-exosomes (MSC-exo). Our aims included evaluation of lung function and pulmonary hypertension in hyperoxia exposed murine animals treated with marijuana exposed and non-exposed preterm MSC-exo.

Design/Methods: The umbilical cords at preterm delivery (24-28 weeks’ gestational age) were collected from 6 marijuana exposed mothers at delivery with 6 non-exposed mothers as control. Marijuana use determined by positive maternal urine THC screen at delivery. The umbilical cord MSCs and their exo generated per published protocols. MSC-exo content analysis performed between two groups. FVB mice placed in hyperoxia (90% O2) within 24 hours of life until day of life 14 when placed back in Normoxia (21% O2). Control animals remained in Normoxia. At day 14, animals injected with 0.1 microgram/g MSC-exo via jugular vein. At day 28, pulmonary function testing and echocardiogram performed to assess lung function and pulmonary hypertension. Human skin epithelium cell-exo used as control.

Results: Marijuana exposed preterm MSC-exo fraction was deficient in lung injury and repair miRNAs when compared with non-exposed preterm MSC-exo fraction (Fig. 1). The marijuana exposed preterm MSC-exo provided partial therapeutic efficacy in hyperoxia exposed animals when compared with marijuana non-exposed preterm MSC-exo. Hyperoxic animals treated with marijuana exposed preterm MSC-exo had lung injury with lower lung inspiratory capacity and compliance compared with marijuana non-exposed preterm MSC-exo (Fig. 2). Similarly, marijuana exposed preterm MSC-exo partially prevented pulmonary hypertension with thickened right ventricular wall and decreased pulmonary artery acceleration time on echocardiogram analysis (Fig. 3). All these results were statistically significant.

Conclusion(s): Maternal marijuana use at the time of delivery alters the biologic potential of human preterm umbilical cord derived MSCs with lack of protected miRNAs involved in lung injury and repair.

Figure 1
miRNA Analysis of Preterm MSC-exo

Figure 2
Lung Function Test in murine animals treated with Preterm MSC-exo

Figure 3
Pulmonary Hypertension in murine animals treated with Preterm MSC-exo