Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Chanèle Cyr-Depauw - , University of Ottawa (Autor:in)
  • David P Cook - , University of Ottawa (Autor:in)
  • Ivana Mižik - , University of Ottawa (Autor:in)
  • Flore Lesage - , University of Ottawa (Autor:in)
  • Arul Vadivel - , Ottawa Hospital Research Institute (Autor:in)
  • Laurent Renesme - , University of Ottawa (Autor:in)
  • Yupu Deng - , Ottawa Health Research Institute, Ottawa, Ontario, Canada. (Autor:in)
  • Shumei Zhong - , University of Ottawa (Autor:in)
  • Pauline Bardin - , Ottawa Hospital Research Institute (Autor:in)
  • Liqun Xu - , Ottawa Hospital Research Institute (Autor:in)
  • Marius A Möbius - , Klinik und Poliklinik für Kinder- und Jugendmedizin, Zentrum für feto-neonatale Gesundheit, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Jenny Marzahn - , Technische Universität Dresden (Autor:in)
  • Daniel Freund - , GMP Facility, Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Duncan J Stewart - , University of Ottawa (Autor:in)
  • Barbara C Vanderhyden - , University of Ottawa (Autor:in)
  • Mario Rüdiger - , Klinik und Poliklinik für Kinder- und Jugendmedizin, Zentrum für feto-neonatale Gesundheit, Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Bernard Thébaud - , Centre hospitalier pour enfants de l'est de l'Ontario (Autor:in)

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

OriginalspracheEnglisch
Seiten (von - bis)814-827
Seitenumfang14
FachzeitschriftAmerican journal of respiratory and critical care medicine
Jahrgang210
Ausgabenummer6
Frühes Online-Datum2 Apr. 2024
PublikationsstatusVeröffentlicht - 15 Sept. 2024
Peer-Review-StatusJa

Externe IDs

unpaywall 10.1164/rccm.202310-1975oc
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