Posters
Academic Level (Author 1)
Medical Student
Discipline Track
Translational Science
Abstract
Introduction: Bronchopulmonary dysplasia (BPD) is a lung disease with high morbidity and mortality in premature neonates exposed to mechanical ventilation and oxygen support. Preclinical studies demonstrate mesenchymal stromal cell (MSC) conditioned media (CdM) improves histologic changes in BPD via the release of paracrine factors. Current modes of administration include intratracheal or intraperitoneal routes with CdM cultured in ambient air.
Objectives: The objective of this study was twofold: (i) assess the efficacy of intranasal delivery of CdM, and (ii) determine whether hypoxic preconditioning stimulates the therapeutic potential of CdM.
Methods: Newborn rat pups were randomly assigned to four groups: (1) room air treated with αMEM vehicle (RA+Veh), (2) four days of hyperoxia (BPD+Veh), (3) BPD treated with CdM from normoxic MSCs (BPD+CdM), and (4) BPD treated with CdM from hypoxic preconditioned (1% O2) MSCs (BPD+hypoCdM). Twenty μL of human mesenchymal stromal cell CdM or hypoxic CdM (hypoCdM) was administered intranasally to rat pups on days 4, 10, and 20. Mean linear intercept, medial wall thickness, and vascular density were used to assess alveolarization, pulmonary remodeling, and vascular growth, respectively. Gene expression of cytokines and growth factors in animal lungs and CdM were measured.
Results and Discussion: Intranasal CdM, but not hypoxic CdM, improved lung alveolarization. Both CdM and hypoCdM improved pulmonary vascular remodeling; however, only hypoCdM restored vascular density. CdM upregulated the expression of genes involved in wound healing and inflammation.
Conclusion: Intranasal delivery of CdM/hypoCdM restored lung development in a BPD rat model. Mechanisms by which umbilical cord-derived stem cell CdM provides pulmonary benefit points toward wound repair and immunomodulation. Future directions include: (i) optimizing the timing, volume, frequency, and concentration of the CdM and (ii) improving the preconditioning approach for MSCs to enhance the therapeutic efficacy.
Acknowledgements: Data were generated in the Flow Cytometry Shared Resource Facility, which is supported by UTHSCSA, NIH-NCI P30 CA054174-20 (Cancer Therapy and Research Center at UTHSCSA) and UL1 TR001129 (Clinical and Translational Science Award). Our gratitude extends to the Pathology Core at UTHSCSA.
Presentation Type
Poster
Recommended Citation
Joy, Jooby; McDaniel, Dawn; Winter, Caitlyn; Noronha, Michelle; Seno, Tyrelle; Winter, Lauryn; Naqvi, Rija; Alayli, Yasmeen; Jones, Maxwell; Mustafa, Shamimunisa; Ahuja, Sunil; and Moreira, Alvaro, "Intranasal Delivery of Human Umbilical Cord Stromal Cell Conditioned Media Improves Alveolar Growth and Vascular Remodeling In Experimental Bronchopulmonary Dysplasia" (2023). Research Colloquium. 11.
https://scholarworks.utrgv.edu/colloquium/presentation/poster/11
Included in
Intranasal Delivery of Human Umbilical Cord Stromal Cell Conditioned Media Improves Alveolar Growth and Vascular Remodeling In Experimental Bronchopulmonary Dysplasia
Introduction: Bronchopulmonary dysplasia (BPD) is a lung disease with high morbidity and mortality in premature neonates exposed to mechanical ventilation and oxygen support. Preclinical studies demonstrate mesenchymal stromal cell (MSC) conditioned media (CdM) improves histologic changes in BPD via the release of paracrine factors. Current modes of administration include intratracheal or intraperitoneal routes with CdM cultured in ambient air.
Objectives: The objective of this study was twofold: (i) assess the efficacy of intranasal delivery of CdM, and (ii) determine whether hypoxic preconditioning stimulates the therapeutic potential of CdM.
Methods: Newborn rat pups were randomly assigned to four groups: (1) room air treated with αMEM vehicle (RA+Veh), (2) four days of hyperoxia (BPD+Veh), (3) BPD treated with CdM from normoxic MSCs (BPD+CdM), and (4) BPD treated with CdM from hypoxic preconditioned (1% O2) MSCs (BPD+hypoCdM). Twenty μL of human mesenchymal stromal cell CdM or hypoxic CdM (hypoCdM) was administered intranasally to rat pups on days 4, 10, and 20. Mean linear intercept, medial wall thickness, and vascular density were used to assess alveolarization, pulmonary remodeling, and vascular growth, respectively. Gene expression of cytokines and growth factors in animal lungs and CdM were measured.
Results and Discussion: Intranasal CdM, but not hypoxic CdM, improved lung alveolarization. Both CdM and hypoCdM improved pulmonary vascular remodeling; however, only hypoCdM restored vascular density. CdM upregulated the expression of genes involved in wound healing and inflammation.
Conclusion: Intranasal delivery of CdM/hypoCdM restored lung development in a BPD rat model. Mechanisms by which umbilical cord-derived stem cell CdM provides pulmonary benefit points toward wound repair and immunomodulation. Future directions include: (i) optimizing the timing, volume, frequency, and concentration of the CdM and (ii) improving the preconditioning approach for MSCs to enhance the therapeutic efficacy.
Acknowledgements: Data were generated in the Flow Cytometry Shared Resource Facility, which is supported by UTHSCSA, NIH-NCI P30 CA054174-20 (Cancer Therapy and Research Center at UTHSCSA) and UL1 TR001129 (Clinical and Translational Science Award). Our gratitude extends to the Pathology Core at UTHSCSA.