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
Seitenumfang14
FachzeitschriftAmerican journal of respiratory and critical care medicine
Jahrgang210
Ausgabenummer6
PublikationsstatusElektronische Veröffentlichung vor Drucklegung - 2 Apr. 2024
Peer-Review-StatusJa

Externe IDs

unpaywall 10.1164/rccm.202310-1975oc

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