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Umbilical cord\u2013derived 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize UC-MSCs\u2019 transcriptome and determine if pregnancy-related complications (preeclampsia and chorioamnionitis) alter their therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>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\u2013cell interactions with neonatal lung cell populations, including NEGR (neuronal growth regulator 1) and NRNX (neurexin) pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202403-0569oc","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T15:10:45Z","timestamp":1732547445000},"page":"391-406","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":11,"title":["Single-Cell RNA Sequencing to Guide Autologous Preterm Cord Mesenchymal Stromal Cell Therapy"],"prefix":"10.1093","volume":"211","author":[{"given":"Chan\u00e8le","family":"Cyr-Depauw","sequence":"first","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine and"},{"name":"Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, 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