Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension.
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2022-08
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Abstract
Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have beneficial effects in preclinical bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) models. The optimal source, dosing, route, and duration of effects are however unknown. The objectives of this study were to (a) compare the efficacy of GMP-grade EVs obtained from Wharton's Jelly MSCs (WJ-MSCs) and bone marrow (BM-MSCs), (b) determine the optimal dosing and route of administration, (c) evaluate its long-term effects, and (d) determine how MSC EVs alter the lung transcriptome. Newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P)1-P14 were given (a) intra-tracheal (IT) BM or WJ-MSC EVs or placebo, (b) varying doses of IT WJ-MSC EVs, or (c) IT or intravenous (IV) WJ-MSC EVs on P3. Rats were evaluated at P14 or 3 months. Early administration of IT BM-MSC or WJ-MSC EVs had similar beneficial effects on lung structure and PH in hyperoxia-exposed rats. WJ-MSC EVs however had superior effects on cardiac remodeling. Low, medium, and high dose WJ-MSC EVs had similar cardiopulmonary regenerative effects. IT and IV WJ-MSC EVs similarly improved vascular density and reduced PH in hyperoxic rats. Gene-set enrichment analysis of transcripts differentially expressed in WJ-MSC EV-treated rats showed that induced transcripts were associated with angiogenesis. Long-term studies demonstrated that a single early MSC EV dose has pulmonary vascular protective effects 3 months after administration. Together, our findings have significant translational implications as it provides critical insight into the optimal source, dosing, route, mechanisms of action, and duration of effects of MSC-EVs for BPD-PH.
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Sharma, Mayank, Michael A Bellio, Merline Benny, Shathiyah Kulandavelu, Pingping Chen, Chawisa Janjindamai, Chenxu Han, Liming Chang, et al. (2022). Mesenchymal Stem Cell-derived Extracellular Vesicles Prevent Experimental Bronchopulmonary Dysplasia Complicated By Pulmonary Hypertension. Stem cells translational medicine, 11(8). pp. 828–840. 10.1093/stcltm/szac041 Retrieved from https://hdl.handle.net/10161/29324.
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Kevin Williams
I've always had an investigative mindset and have always loved sharing my knowledge with others. I've spent time in basic science settings working on stem cells and and published on their role in neonatal lung injury, this systemic approach to problem analysis and resolution has provided me with the framework that I use for medical education. This passion has guided my path in medicine both in practice as a neonatologist and in my work in medical education as a tutor, simulation-based educator and mentor.
I have received regional and national recognition for my basic science work and recognition as a resident and fellow for my excellence in teaching and mentorship while at the University of Miami. I plan to continue this work looking at interdisciplinary training in simulation and expanding access and use to point-of-care US in the neonatal ICU setting. There is so much to be done in these areas, and I am excited to play a role in getting it done!
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