Refractory acute graft-versus-host disease (GVHD) occurs when the immune injury exceeds the capacity of injured tissues to regenerate and repair. While glucocorticoids have been used for decades to treat GVHD, Arnhold, Chang, and colleagues in this issue of the JCI question whether this approach can in fact be counterproductive. Using in vivo experimental models of GVHD and in vitro intestinal organoids, the study authors show that glucocorticoid exposure directly impeded small intestinal epithelial proliferation and survival, thus preventing the resolution of injury. These findings suggest that future treatment approaches for acute GVHD should include measures to reduce immune reactivity as well as interventions to actively promote tissue resilience.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977979 | PMC |
| http://dx.doi.org/10.1172/JCI177728 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.
Cytotherapy
January 2025
Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Ontario, Canada. Electronic address:
The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.
View Article and Find Full Text PDFFecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.
Nat Commun
January 2025
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.
View Article and Find Full Text PDFGastrointestinal Disease in Common Variable Immunodeficiency Disorder (CVID): Histological Patterns, Diagnostic Clues and Pitfalls for the Pathologist and Gastroenterologist.
J Clin Med
January 2025
Department of Pathology, Ghent University Hospital, Ghent University, 9000 Ghent, Belgium.
: Gastrointestinal diseases are a major cause of morbidity in common variable immunodeficiency disorder (CVID), clinically often mimicking other conditions including celiac disease and inflammatory bowel disease (IBD). Hence, diagnosis of CVID remains challenging. This study aims to raise awareness and highlight histopathological clues for CVID in intestinal biopsies, emphasizing diagnostic pitfalls for the pathologist/gastroenterologist.
View Article and Find Full Text PDFEstablishment of iPSC-Derived MSCs Expressing hsa-miR-4662a-5p for Enhanced Immune Modulation in Graft-Versus-Host Disease (GVHD).
Int J Mol Sci
January 2025
Catholic High-Performance Cell Therapy Center & Department of Medical Life Science, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 06591, Republic of Korea.
The immune-modulatory effects of mesenchymal stromal cells (MSCs) are widely used to treat inflammatory disorders, with indoleamine 2,4-dioxygenase-1 (IDO-1) playing a pivotal role in suppressing stimulated T-cell proliferation. Taking that three-dimensional (3D) cultures enhance MSCs' anti-inflammatory properties compared with two-dimensional (2D) cultures, the differentially expressed miRNAs were examined. Thus, we identified hsa-miR-4662a-5p (miR-4662a) as a key inducer of IDO-1 via its suppression of bridging integrator-1 (BIN-1), a negative regulator of the IDO-1 gene.
View Article and Find Full Text PDFComparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Older Versus Younger Patients.
Cancers (Basel)
January 2025
Department of Bone Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
Background: Previous studies have shown that allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA haploidentical (haplo) donor followed by graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) results in lower relapse rates and improved DFS when compared to haplo bone marrow transplant (BMT) with PTCy. However, PBSCT leads to higher rates of GVHD. It is unknown whether the benefits of haplo PBSCT may be nullified in older patients (>60 years) by a higher susceptibility to GVHD and transplant related toxicity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!