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Restoring hematopoietic stem and progenitor cell function in mice by delivery of RNA lipid nanoparticles.
Mol Ther Nucleic Acids
March 2025
Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Fanconi anemia (FA) is a congenital multisystem disorder characterized by early-onset bone marrow failure (BMF) and cancer susceptibility. While gene addition and repair therapies are being considered as treatment options, depleted hematopoietic stem cell (HSC) pools, poor HSC mobilization, compromised survival during transduction, and increased sensitivity to conventional conditioning strategies limit eligibility for FA patients to receive gene therapies. As an alternative approach, we explored protein replacement by mRNA delivery via lipid nanoparticles (LNPs).
View Article and Find Full Text PDFIntrafemoral Injection of Human Hematopoietic Stem and Progenitor Cells into Immunocompromised Mice.
J Vis Exp
December 2023
Wellcome and Medical Research Council Cambridge Stem Cell Institute, Department of Haematology, University of Cambridge;
Hematopoietic stem cells (HSCs) are defined by their lifelong ability to produce all blood cell types. This is operationally tested by transplanting cell populations containing HSCs into syngeneic or immunocompromised mice. The size and multilineage composition of the graft is then measured over time, usually by flow cytometry.
View Article and Find Full Text PDFSimplified Intrafemoral Injections Using Live Mice Allow for Continuous Bone Marrow Analysis.
J Vis Exp
November 2023
Department of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine;
Despite the complexity of hematopoietic cell transplantation in humans, researchers commonly perform intravenous or intrafemoral (IF) injections in mice. In murine models, this technique has been adapted to enhance the seeding efficiency of transplanted hematopoietic stem and progenitor cells (HSPCs). This paper describes a detailed step-by-step technical procedure of IF injection and the following bone marrow (BM) aspiration in mice that allows for serial characterization of cells present in the BM.
View Article and Find Full Text PDFTetrazine-Derived Near-Infrared Dye for Targeted Photoacoustic Imaging of Bone.
J Med Chem
May 2023
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
A near-infrared photoacoustic probe was used to image bone through active and bioorthogonal pretargeting strategies that utilized coupling between a tetrazine-derived cyanine dye and a -cyclooctene-modified bisphosphonate. hydroxyapatite binding of the probe active and pretargeting strategies showed comparable increases in percent binding a nontargeted control. Intrafemoral injection of the bisphosphonate-dye conjugate showed retention out to 24 h post-injection, with a 14-fold increase in signal over background, while the nontargeted dye exhibited negligible binding to bone and signal washout by 4 h post-injection.
View Article and Find Full Text PDFSpleen route accelerates engraftment of human hematopoietic stem cells.
Biochem Biophys Res Commun
September 2021
Université de Bordeaux, Bordeaux, France; INSERM U1035, Bordeaux, France; CHU de Bordeaux, Bordeaux, France.
Intravenous injections of human hematopoietic stem cells (hHSCs) is routinely used in clinic and for modeling hematopoiesis in mice. However, unspecific dilution in vascular system and non-hematopoietic organs challenges engraftment efficiency. Although spleen is capable of extra medullar hematopoiesis, its ability to support human HSC transplantation has never been evaluated.
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