Biomolecules
Division of Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St Louis, MO 63105, USA.
Published: August 2024
The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and the subsequent regeneration of stable trilineage hematopoiesis in a timely manner. Granulocyte-colony-stimulating factor (G-CSF) is currently the most frequently used agent for HSPC mobilization. However, it requires five or more daily infusions to produce an adequate number of HSPCs and the use of G-CSF alone often results in suboptimal stem cell yields in a significant number of patients. Furthermore, there are several undesirable side effects associated with G-CSF, and it is contraindicated for use in sickle-cell anemia patients, where it has been linked to serious vaso-occlusive and thrombotic events. The chemokine receptor CXCR4 and the cell surface integrin α4β1 (very late antigen 4 (VLA4)) are both involved in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of the CXCR4 or VLA4 receptors with their endogenous ligands within the bone marrow niche results in the rapid and reversible mobilization of HSPCs into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the roles CXCR4 and VLA4 play in bone marrow homing and retention and will summarize more recent development of small-molecule CXCR4 and VLA4 inhibitors that, when combined, can synergistically improve the magnitude, quality and convenience of HSPC mobilization for stem cell transplantation and ex vivo gene therapy after the administration of just a single dose. This optimized regimen has the potential to afford a superior alternative to G-CSF for HSPC mobilization.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11353233 | PMC |
http://dx.doi.org/10.3390/biom14081003 | DOI Listing |
Nucleosides Nucleotides Nucleic Acids
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Division of Hematology, Department of Internal Medicine, Medical Faculty, Tekirdağ Namık Kemal University, Tekirdağ, Turkey.
Breast cancer is the most common malignancy that affects women. MicroRNAs (miRNAs) play an essential role in cancer therapy and regulate many biological processes such as cisplatin resistance. The study's objective was to determine whether miR-182 dysregulation was the cause of cisplatin resistance in TNBC cell line MDA-MB-231.
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March 2025
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Background: Midfoot pain is common but poorly understood, with radiographs often indicating no anomalies. This study aimed to describe bone, joint and soft tissue changes and to explore associations between MRI-detected abnormalities and clinical symptoms (pain and disability) in a group of adults with midfoot pain, but who were radiographically negative for osteoarthritis.
Methods: Community-based participants with midfoot pain underwent an MRI scan of one foot and scored semi-quantitatively using the Foot OsteoArthritis MRI Score (FOAMRIS).
J Biomed Mater Res B Appl Biomater
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The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA.
The formation of fibrocartilage in microfracture (MFX) severely limits its long-term outlook. There is consensus in the scientific community that the placement of an appropriate scaffold in the MFX defect site can promote hyaline cartilage formation and improve therapeutic benefit. Accordingly, in this work, a novel natural biomaterial-the cartilage analog (CA)-which met criteria favorable for chondrogenesis, was evaluated in vitro to determine its candidacy as a potential MFX scaffold.
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Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Falmer, Brighton BN1 9PX, UK.
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Department of Hematology and Bone Marrow Transplant, National Center for Cancer Care and Research, Doha P.O. Box 3050, Qatar.
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