ArticleHaematologica2021
Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07740499 (Exploring and Exploiting the TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells to Cure Pediatric Inflammatory Bowel Disease), which is not on this map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Exploring and Exploiting the TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells to Cure Pediatric Inflammatory Bowel Disease
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis.Blood · 2024Trial
- Ex vivo expansion of hematopoietic stem and progenitor cells from human mobilized peripheral blood for gene therapy applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- A p38 MAPK-ROS axis fuels proliferation stress and DNA damage during CRISPR-Cas9 gene editing in hematopoietic stem and progenitor cells.Cell reports. Medicine · 2024Article
- Correction of osteopetrosis in the neonateFrontiers in endocrinology · 2024Article
- Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.Current medicinal chemistry · 2024Review
- Comparison of osteoclast differentiation protocols from human induced pluripotent stem cells of different tissue origins.Stem cell research & therapy · 2023Article
- Comparison of osteoclast differentiation protocols from human induced pluripotent stem cells of different tissue origins.Research square · 2023Article
- Molecular Mechanisms of Craniofacial and Dental Abnormalities in Osteopetrosis.International journal of molecular sciences · 2023Review
- Outlining the Clinical Profile ofGenes · 2023Article
- Human Hematopoietic Stem Cells Co-cultured in 3D with Stromal Support to Optimize Lentiviral Vector-mediated Gene Transduction.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Interstitial Lung Disease in Immunocompromised Children.Diagnostics (Basel, Switzerland) · 2022Article
- New Insights into Hematopoietic Stem Cell Expansion to Stimulate Repopulation of the Adult Blood System for Transplantation.Life (Basel, Switzerland) · 2022Review
- Review
- Recombinant Limb Assay asFrontiers in cell and developmental biology · 2022Article
- Clinical and molecular characterization of five Chinese patients with autosomal recessive osteopetrosis.Molecular genetics & genomic medicine · 2021Article
- The V-ATPaseInternational journal of molecular sciences · 2021Review
- Autosomal recessive osteopetrosis: mechanisms and treatments.Disease models & mechanisms · 2021Review
- Gene therapy for infantile malignant osteopetrosis: review of pre-clinical research and proof-of-concept for phenotypic reversal.Molecular therapy. Methods & clinical development · 2021Review
- Subtrochanteric Femoral Fracture in a Patient with Osteopetrosis: Treated with Internal Fixation and Complicated by Intraoperative Femoral Neck Fracture.International journal of general medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 15 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allogeneic hematopoietic stem cell transplantation is the treatment of choice for autosomal recessive osteopetrosis caused by defects in the TCIRG1 gene. Despite recent progress in conditioning, a relevant number of patients are not eligible for allogeneic stem cell transplantation because of the severity of the disease and significant transplant-related morbidity. We exploited peripheral CD34+ cells, known to circulate at high frequency in the peripheral blood of TCIRG1-deficient patients, as a novel cell source for autologous transplantation of gene corrected cells. Detailed phenotypical analysis showed that circulating CD34+ cells have a cellular composition that resembles bone marrow, supporting their use in gene therapy protocols. Transcriptomic profile revealed enrichment in genes expressed by hematopoietic stem and progenitor cells (HSPCs). To overcome the limit of bone marrow harvest/ HSPC mobilization and serial blood drawings in TCIRG1 patients, we applied UM171-based ex-vivo expansion of HSPCs coupled with lentiviral gene transfer. Circulating CD34+ cells from TCIRG1-defective patients were transduced with a clinically-optimized lentiviral vector (LV) expressing TCIRG1 under the control of phosphoglycerate promoter and expanded ex vivo. Expanded cells maintained long-term engraftment capacity and multi-lineage repopulating potential when transplanted in vivo both in primary and secondary NSG recipients. Moreover, when CD34+ cells were differentiated in vitro, genetically corrected osteoclasts resorbed the bone efficiently. Overall, we provide evidence that expansion of circulating HSPCs coupled to gene therapy can overcome the limit of stem cell harvest in osteopetrotic patients, thus opening the way to future gene-based treatment of skeletal diseases caused by bone marrow fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.