title: Gene Therapy with Hematopoietic Stem Cells: The Diseased Bone Marrow's Point of View.
abstract: When considering inherited diseases that can be treated by gene transfer into hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and adrenoleukodystrophy (ALD). In all other settings [X-linked severe combined immunodeficiency (X-SCID), adenosine deaminase deficiency, Wiskott-Aldrich syndrome, and β-hemoglobinopathies], the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics. These peculiarities can influence the cells' harvesting and behavior in culture, and the postgraft uptake and further behavior of the gene-modified hematopoietic/precursor cells. In the present mini-review, we shall briefly summarize these characteristics and outline the possible consequences and challenges.
authors.affiliation: 1 Biotherapy Department, Necker Children's Hospital , Assistance Publique-Hôpitaux de Paris, Paris, France .|2 Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM , Paris, France .|3 Paris Descartes-Sorbonne Paris Cité University , Imagine Institute, Paris, France .|4 Laboratory of Human Lymphohematopoiesis, INSERM UMR 1163 , Paris, France .
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana
authors.affiliation: 1 Biotherapy Department, Necker Children's Hospital , Assistance Publique-Hôpitaux de Paris, Paris, France .
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Ribeil
authors.affiliation: 2 Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM , Paris, France .|3 Paris Descartes-Sorbonne Paris Cité University , Imagine Institute, Paris, France .|4 Laboratory of Human Lymphohematopoiesis, INSERM UMR 1163 , Paris, France .
authors.forename: Chantal
authors.initials: C
authors.lastname: Lagresle-Peyrou
authors.affiliation: 2 Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM , Paris, France .|3 Paris Descartes-Sorbonne Paris Cité University , Imagine Institute, Paris, France .|4 Laboratory of Human Lymphohematopoiesis, INSERM UMR 1163 , Paris, France .
authors.forename: Isabelle
authors.initials: I
authors.lastname: André-Schmutz
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D001855:Bone Marrow Diseases / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans
keywords: HSC; bone marrow; gene therapy