Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
RATIONALE: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. Results of clinical trials with MSCs for many disorders do not yet match the promising preclinical studies. A lack of specific criteria to define functionally distinct MSCs persists.
OBJECTIVES: To determine and correlate single-cell UC-MSC transcriptomic profile with therapeutic potential.
METHODS: UC-MSCs from five term donors and human neonatal dermal fibroblasts (HNDFs, control cells of mesenchymal origin) transcriptomes were investigated by single-cell RNA sequencing analysis (scRNA-seq). The lung-protective effect of UC-MSCs with a distinct transcriptome and control HNDFs was tested in vivo in hyperoxia-induced neonatal lung injury in rats.
MEASUREMENTS AND MAIN RESULTS: UC-MSCs showed limited transcriptomic heterogeneity, but were different from HNDFs. Gene ontology enrichment analysis revealed distinct - progenitor-like and fibroblast-like - UC-MSC subpopulations. Only the treatment with progenitor-like UC-MSCs improved lung function and structure and attenuated pulmonary hypertension in hyperoxia-exposed rat pups. Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of non-therapeutic cells and associated with decreased lung retention.
CONCLUSIONS: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 814-827 |
Seitenumfang | 14 |
Fachzeitschrift | American journal of respiratory and critical care medicine |
Jahrgang | 210 |
Ausgabenummer | 6 |
Frühes Online-Datum | 2 Apr. 2024 |
Publikationsstatus | Veröffentlicht - 15 Sept. 2024 |
Peer-Review-Status | Ja |
Externe IDs
unpaywall | 10.1164/rccm.202310-1975oc |
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Scopus | 85200997077 |
Schlagworte
Ziele für nachhaltige Entwicklung
Schlagwörter
- Animals, Bronchopulmonary Dysplasia/genetics, Disease Models, Animal, Humans, Infant, Newborn, Mesenchymal Stem Cell Transplantation/methods, Mesenchymal Stem Cells, Rats, Sequence Analysis, RNA, Single-Cell Analysis/methods, Transcriptome, Umbilical Cord/cytology