Foundry120 atlas

← IBD single-cell transcriptomics

The reparative immunologic consequences of stem cell transplantation as a cellular therapy for refractory Crohn’s disease

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Dataset overview

Participants 19
Samples 36
Reuse readiness 6.0/10 evidence-backed score

Reparative immunological consequences of stem cell transplantation as a cellular therapy for refractory Crohn's disease.

Guisado D, Talware S, Wang X, Davis A, Fozilov E, Etra A, Colombel JF, Schaniel C, et al. · Gut · 2025

Abstract

<h4>Background</h4>Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown.<h4>Objective</h4>The objective of this study is to understand how the immune system reconstitutes post-SCT and whether SCT may function as a cellular therapy restoring appropriately responsive immune cell populations from haematopoietic stem cells (HSCs).<h4>Design</h4>Adults with CD with active clinical and endoscopic disease who failed available medical therapies were enrolled in a phase II study of SCT for refractory CD (n=19). Blood and intestinal samples were collected longitudinally and analysed using CyTOF and scRNA-seq. Stem cell autografts were functionally assayed in mouse xenograft models.<h4>Results</h4>scRNA-seq and CyTOF analyses reveal that SCT predominantly affected the intestinal myeloid lineage with loss of inflammatory populations and return of macrophages capable of supporting mucosal healing. Xenograft models using patient HSCs suggested that HSCs support the early reconstitution of the myeloid lineage and reveal an impairment of short and long-term HSC engraftment that may determine SCT outcomes.<h4>Conclusions</h4>This study suggests SCT functions as a myeloid-directed cellular therapy reinforcing the critical role of macrophages in refractory CD pathophysiology and as a target for cellular therapies. Furthermore, we report an unrecognised functional heterogeneity among HSC subpopulations in CD that may be relevant to our understanding of CD treatment and pathophysiology.

doi:10.1136/gutjnl-2024-333558 ↗ PMID 39961646 ↗ PMC12513369 ↗

Study facts

Organism
Homo sapiens
Platform
10x Genomics Chromium iX and Illumina NovaSeq 6000
Age group
adult
Disease groups
—
Anatomical sites
—

Data availability

  • Processed matrix

File types MTXTSV

Strengths & limitations for reuse

Strengths

  • Processed matrices are advertised
  • Participant mapping is available
  • Participant counts are documented

Limitations

  • Not documented: raw counts are advertised
  • Not documented: cell metadata are advertised
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.assay_type single-cell RNA sequencing
processed for 10x Genomics single cell RNA sequencing (scRNA-seq)

Section series, offset —
assay.library_chemistry 10x Genomics Chromium Single Cell 3′ v3.1
processed using the 10x Genomics Chromium Single Cell 3′ v3.1 kit

Section samples, offset —
assay.platform 10x Genomics Chromium iX and Illumina NovaSeq 6000
run on the 10x Genomics Chromium iX instrument

Section samples, offset —
assay.reference_genome GRCh38
Assembly: GRCh38

Section samples, offset —
assay.sequencing_type scrna_seq
samples at baseline and 6 months post-SCT were analysed with scRNA-seq

Section Results, offset —

Cohort

FieldValueEvidence
cohort.age_group adult
Design Adults with CD with active clinical and endoscopic disease

Section geo_record_summary, offset —
cohort.crohns_disease_participants 19
19 patients were enrolled from 2018 to 2023

Section Results, offset —
cohort.disease_activity_metadata_available True
Patients with medically refractory CD were enrolled in the MASCT-CD trial.

Section Results, offset —
cohort.study_design longitudinal
Blood and intestinal samples were collected longitudinally

Section geo_record_summary, offset —
cohort.total_participants 19
19 patients were enrolled from 2018 to 2023

Section Results, offset —
cohort.treatment_exposure_documented True
Patients with medically refractory CD were enrolled in the MASCT-CD trial.

Section Results, offset —
cohort.treatment_response_metadata_available True
At 6 months post-transplant 10/14 patients had an endoscopic remission

Section Results, offset —

Data_Assets

FieldValueEvidence
data_assets.open_access True
Data are available in a public, open access repository.

Section Data availability statement, offset —
data_assets.processed_matrix True
Supplementary files format and content: tab-separated value files and matrix files

Section samples, offset —

Processing

FieldValueEvidence
processing.cell_type_annotation_method Known marker genes and reference datasets
Single cells were clustered and annotated using known sets of marker genes and reference data sets

Section Results, offset —
processing.quality_control_reported True
FASTQ files underwent processing through the Cellranger Count v6.1.1 pipeline for quality control

Section samples, offset —

Specimens

FieldValueEvidence
specimens.inflamed_status_available True
patients with histological inflammation had persistent suppression of CD14 + populations

Section Results, offset —
specimens.number_of_samples 36
"n_samples": 36

Section geo_record_summary, offset —
specimens.participant_to_sample_mapping_available True
"title": "PT18 ileum baseline"

Section geo_record_summary, offset —
specimens.specimen_type biopsy
Samples of tissue from endoscopic biopsies, peripheral blood and peripheral mobilized stem cells were collected

Section series, offset —