ArticleThe Journal of clinical investigation2019
Bone marrow stromal cells from β-thalassemia patients have impaired hematopoietic supportive capacity.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Safety and pharmacodynamics of the ferroportin inhibitor vamifeport in patients with non-transfusion-dependent β-thalassemia: results from a randomized phase 2a study.Orphanet journal of rare diseases · 2025Trial
- Update of the decision-making algorithm on selecting transfusion-dependent β-thalassemic patients for gene therapy approaches: joint consensus report on behalf of EHA-specialized working group and EBMT hemoglobinopathies working party.Bone marrow transplantation · 2026Article
- Article
- Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche.Cell reports. Medicine · 2025Review
- Leukemic Cells Hijack Stromal Bioelectricity to Reprogram the Bone Marrow Niche via CaV1.2-Dependent Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- In transfusion-dependent thalassemia, neuronal damage biomarkers are associated with affective and chronic fatigue symptoms.Scientific reports · 2025Article
- Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.Nature communications · 2025Article
- Early bone marrow alterations in patients with adenosine deaminase 2 deficiency across disease phenotypes and severities.The Journal of allergy and clinical immunology · 2025Article
- CRISPR/Cas-edited iPSCs and mesenchymal stem cells: a concise review of their potential in thalassemia therapy.Frontiers in cell and developmental biology · 2025Review
- Article
- The influence of iron on bone metabolism disorders.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Review
- Exploring the bone marrow micro environment in thalassemia patients: potential therapeutic alternatives.Frontiers in immunology · 2024Review
- Reduced proliferation of bone marrow MSC after allogeneic stem cell transplantation is associated with clinical outcome.Blood advances · 2023Article
- Extracellular Hemoglobin: Modulation of Cellular Functions and Pathophysiological Effects.Biomolecules · 2022Review
- Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients.Bone marrow transplantation · 2022Article
- Targeting the Hematopoietic Stem Cell Niche in β-Thalassemia and Sickle Cell Disease.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Article
- The EHA Research Roadmap: Normal Hematopoiesis.HemaSphere · 2021Article
- Editing outside the body: Ex vivo gene-modification for β-hemoglobinopathy cellular therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe human bone marrow (BM) niche contains a population of mesenchymal stromal cells (MSCs) that provide physical support and regulate hematopoietic stem cell (HSC) homeostasis. β-Thalassemia (BT) is a hereditary disorder characterized by altered hemoglobin beta-chain synthesis amenable to allogeneic HSC transplantation and HSC gene therapy. Iron overload (IO) is a common complication in BT patients affecting several organs. However, data on the BM stromal compartment are scarce.
methodsMSCs were isolated and characterized from BM aspirates of healthy donors (HDs) and BT patients. The state of IO was assessed and correlated with the presence of primitive MSCs in vitro and in vivo. Hematopoietic supportive capacity of MSCs was evaluated by transwell migration assay and 2D coculture of MSCs with human CD34+ HSCs. In vivo, the ability of MSCs to facilitate HSC engraftment was tested in a xenogenic transplant model, whereas the capacity to sustain human hematopoiesis was evaluated in humanized ossicle models.
resultsWe report that, despite iron chelation, BT BM contains high levels of iron and ferritin, indicative of iron accumulation in the BM niche. We found a pauperization of the most primitive MSC pool caused by increased ROS production in vitro which impaired MSC stemness properties. We confirmed a reduced frequency of primitive MSCs in vivo in BT patients. We also discovered a weakened antioxidative response and diminished expression of BM niche-associated genes in BT-MSCs. This caused a functional impairment in MSC hematopoietic supportive capacity in vitro and in cotransplantation models. In addition, BT-MSCs failed to form a proper BM niche in humanized ossicle models.
conclusionOur results suggest an impairment in the mesenchymal compartment of BT BM niche and highlight the need for novel strategies to target the niche to reduce IO and oxidative stress before transplantation.
fundingThis work was supported by the SR-TIGET Core grant from Fondazione Telethon and by Ricerca Corrente.
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