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Single-cell RNA sequencing to guide autologous preterm cord mesenchymal stromal cell therapy

Rationale: The chronic lung disease bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity (<28 wk of gestation). Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an opportunity for autologous cell therapy, as UC-MSCs have been shown to im...

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Main Authors: Cyr-Depauw, Chanèle (Author) , Mižíková, Ivana (Author) , Cook, David P. (Author) , Lesage, Flore (Author) , Vadivel, Arul (Author) , Renesme, Laurent (Author) , Deng, Yupu (Author) , Zhong, Shumei (Author) , Bardin, Pauline (Author) , Xu, Liqun (Author) , Möbius, Marius A. (Author) , Marzahn, Jenny (Author) , Freund, Daniel (Author) , Stewart, Duncan J. (Author) , Vanderhyden, Barbara C. (Author) , Rüdiger, Mario (Author) , Thébaud, Bernard (Author)
Format: Article (Journal)
Language:English
Published: 2025
In: American journal of respiratory and critical care medicine
Year: 2025, Volume: 211, Issue: 3, Pages: 391-406
ISSN:1535-4970
DOI:10.1164/rccm.202403-0569OC
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1164/rccm.202403-0569OC
Verlag, lizenzpflichtig, Volltext: https://www.atsjournals.org/doi/10.1164/rccm.202403-0569OC
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Author Notes:Chanèle Cyr-Depauw, Ivana Mižik, David P. Cook, Flore Lesage, Arul Vadivel, Laurent Renesme, Yupu Deng, Shumei Zhong, Pauline Bardin, Liqun Xu, Marius A. Möbius, Jenny Marzahn, Daniel Freund, Duncan J. Stewart, Barbara C. Vanderhyden, Mario Rüdiger, Bernard Thébaud
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Summary:Rationale: The chronic lung disease bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity (<28 wk of gestation). Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an opportunity for autologous cell therapy, as UC-MSCs have been shown to improve lung function and structure in experimental BPD. However, characterization and repair capacity of UC-MSCs derived from donors with pregnancy-related complications associated with prematurity remain unexplored. - - Objectives: To characterize UC-MSCs’ transcriptome and determine if pregnancy-related complications (preeclampsia and chorioamnionitis) alter their therapeutic potential. - - Methods: Single-cell RNA sequencing was used to compare the transcriptome of UC-MSCs derived from 5 term donors, 16 preterm donors, and human neonatal dermal fibroblasts (control cells of mesenchymal origin) and correlated with their therapeutic potential in experimental BPD. Using publicly available neonatal lung single-nucleus RNA sequencing data, we also determined putative communication networks between UC-MSCs and resident lung cell populations. - - Measurements and Main Results: Most UC-MSCs displayed a similar transcriptome despite their pregnancy-related conditions and mitigated hyperoxia-induced lung injury in newborn rats. Conversely, human neonatal dermal fibroblasts and one term and two preterm with preeclampsia UC-MSC donors exhibited a distinct transcriptome enriched in genes related to fibroblast function and senescence and were devoid of therapeutic benefit in hyperoxia-induced BPD. Conversely, therapeutic UC-MSCs displayed a unique transcriptome active in cell proliferation and distinct cell-cell interactions with neonatal lung cell populations, including NEGR (neuronal growth regulator 1) and NRNX (neurexin) pathways. - - Conclusions: Term and preterm UC-MSCs are lung protective in experimental BPD. Single-cell RNA sequencing allows us to identify donors with a distinct UC-MSC transcriptome characteristic of reduced therapeutic potential.
Item Description:Gesehen am 08.09.2025
Physical Description:Online Resource
ISSN:1535-4970
DOI:10.1164/rccm.202403-0569OC

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