Multipotent adult progenitor cells prevent functional impairment and improve development in inflammation driven detriment of preterm ovine lungs.

Autor:	Neuen SML; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Ophelders DRMG; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Widowski H; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.; Department of BioMedical Engineering, Maastricht University, Maastricht, the Netherlands., Hütten MC; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Brokken T; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., van Gorp C; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands., Nikkels PGJ; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands., Severens-Rijvers CAH; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.; Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands., Sthijns MMJPE; Food Innovation and Health, Department of Human Biology, Maastricht University, Venlo, the Netherlands.; NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.; MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, the Netherlands., van Blitterswijk CA; MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, the Netherlands., Troost FJ; Food Innovation and Health, Department of Human Biology, Maastricht University, Venlo, the Netherlands., LaPointe VLS; MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, the Netherlands., Jolani S; Department of Methodology and Statistics, School CAPHRI, Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands., Seiler C; Department of Advanced Computing Sciences, Maastricht University, Maastricht, the Netherlands.; Mathematics Centre Maastricht, Maastricht University, the Netherlands., Pillow JJ; School of Human Sciences, University of Western Australia, Perth, WA, Australia., Delhaas T; Department of BioMedical Engineering, Maastricht University, Maastricht, the Netherlands.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands., Reynaert NL; NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.; Department of Respiratory Medicine, Maastricht University, Maastricht, the Netherlands., Wolfs TGAM; Department of Pediatrics, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, the Netherlands.; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
Jazyk:	angličtina
Zdroj:	Regenerative therapy [Regen Ther] 2024 Mar 28; Vol. 27, pp. 207-217. Date of Electronic Publication: 2024 Mar 28 (Print Publication: 2024).
DOI:	10.1016/j.reth.2024.03.014
Abstrakt:	Background: Perinatal inflammation increases the risk for bronchopulmonary dysplasia in preterm neonates, but the underlying pathophysiological mechanisms remain largely unknown. Given their anti-inflammatory and regenerative capacity, multipotent adult progenitor cells (MAPC) are a promising cell-based therapy to prevent and/or treat the negative pulmonary consequences of perinatal inflammation in the preterm neonate. Therefore, the pathophysiology underlying adverse preterm lung outcomes following perinatal inflammation and pulmonary benefits of MAPC treatment at the interface of prenatal inflammatory and postnatal ventilation exposures were elucidated. Methods: Instrumented ovine fetuses were exposed to intra-amniotic lipopolysaccharide (LPS 5 mg) at 125 days gestation to induce adverse systemic and peripheral organ outcomes. MAPC (10 × 10 6  cells) or saline were administered intravenously two days post LPS exposure. Fetuses were delivered preterm five days post MAPC treatment and either killed humanely immediately or mechanically ventilated for 72 h. Results: Antenatal LPS exposure resulted in inflammation and decreased alveolar maturation in the preterm lung. Additionally, LPS-exposed ventilated lambs showed continued pulmonary inflammation and cell junction loss accompanied by pulmonary edema, ultimately resulting in higher oxygen demand. MAPC therapy modulated lung inflammation, prevented loss of epithelial and endothelial barriers and improved lung maturation in utero . These MAPC-driven improvements remained evident postnatally, and prevented concomitant pulmonary edema and functional loss. Conclusion: In conclusion, prenatal inflammation sensitizes the underdeveloped preterm lung to subsequent postnatal inflammation, resulting in injury, disturbed development and functional impairment. MAPC therapy partially prevents these changes and is therefore a promising approach for preterm infants to prevent adverse pulmonary outcomes. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)
Databáze:	MEDLINE
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