Cargando…
Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates
Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985113/ https://www.ncbi.nlm.nih.gov/pubmed/36724000 http://dx.doi.org/10.1093/stcltm/szac088 |
_version_ | 1784900884418789376 |
---|---|
author | Möbius, Marius A Seidner, Steven R McCurnin, Donald C Menschner, Leonhard Fürböter-Behnert, Isabel Schönfeld, Julia Marzahn, Jenny Freund, Daniel Münch, Nadine Hering, Sandra Mustafa, Shamimunisa B Anzueto, Diana G Winter, Lauryn A Blanco, Cynthia L Hanes, Martha A Rüdiger, Mario Thébaud, Bernard |
author_facet | Möbius, Marius A Seidner, Steven R McCurnin, Donald C Menschner, Leonhard Fürböter-Behnert, Isabel Schönfeld, Julia Marzahn, Jenny Freund, Daniel Münch, Nadine Hering, Sandra Mustafa, Shamimunisa B Anzueto, Diana G Winter, Lauryn A Blanco, Cynthia L Hanes, Martha A Rüdiger, Mario Thébaud, Bernard |
author_sort | Möbius, Marius A |
collection | PubMed |
description | Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms. |
format | Online Article Text |
id | pubmed-9985113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99851132023-03-05 Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates Möbius, Marius A Seidner, Steven R McCurnin, Donald C Menschner, Leonhard Fürböter-Behnert, Isabel Schönfeld, Julia Marzahn, Jenny Freund, Daniel Münch, Nadine Hering, Sandra Mustafa, Shamimunisa B Anzueto, Diana G Winter, Lauryn A Blanco, Cynthia L Hanes, Martha A Rüdiger, Mario Thébaud, Bernard Stem Cells Transl Med Fetal and Neonatal Stem Cells Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms. Oxford University Press 2023-02-01 /pmc/articles/PMC9985113/ /pubmed/36724000 http://dx.doi.org/10.1093/stcltm/szac088 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Fetal and Neonatal Stem Cells Möbius, Marius A Seidner, Steven R McCurnin, Donald C Menschner, Leonhard Fürböter-Behnert, Isabel Schönfeld, Julia Marzahn, Jenny Freund, Daniel Münch, Nadine Hering, Sandra Mustafa, Shamimunisa B Anzueto, Diana G Winter, Lauryn A Blanco, Cynthia L Hanes, Martha A Rüdiger, Mario Thébaud, Bernard Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates |
title | Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates |
title_full | Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates |
title_fullStr | Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates |
title_full_unstemmed | Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates |
title_short | Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates |
title_sort | prophylactic administration of mesenchymal stromal cells does not prevent arrested lung development in extremely premature-born non-human primates |
topic | Fetal and Neonatal Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985113/ https://www.ncbi.nlm.nih.gov/pubmed/36724000 http://dx.doi.org/10.1093/stcltm/szac088 |
work_keys_str_mv | AT mobiusmariusa prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT seidnerstevenr prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT mccurnindonaldc prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT menschnerleonhard prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT furboterbehnertisabel prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT schonfeldjulia prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT marzahnjenny prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT freunddaniel prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT munchnadine prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT heringsandra prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT mustafashamimunisab prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT anzuetodianag prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT winterlauryna prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT blancocynthial prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT hanesmarthaa prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT rudigermario prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates AT thebaudbernard prophylacticadministrationofmesenchymalstromalcellsdoesnotpreventarrestedlungdevelopmentinextremelyprematurebornnonhumanprimates |