title: Innovative cell therapy in the treatment of serious adverse events related to both chemo-radiotherapy protocol and acute myeloid leukemia syndrome: the infusion of mesenchymal stem cells post-treatment reduces hematopoietic toxicity and promotes hematopoietic reconstitution.
abstract: Bone marrow stroma is damaged by chemotherapy and irradiation protocol. Bone marrow microenvironment supports haematopoiesis and comprises Mesenchymal Stem Cells (MSCs). Coinfusion of MSCs with hematopoietic stem cells (HSC) improves engraftment and accelerates haematopoietic recovery. Stroma-derived factor-1 (SDF-1) is a chemotactic factor which plays a crucial role in stem cell transplantation by enhancing the ability of HSC to engraft. In this study expression of SDF-1 in bone marrow MSCs and the level of Colony Forming Unit Fibroblast (CFU-F) were evaluated in 8 patients with Acute Myeloid leukemia (AML). Evaluation was done at diagnosis and after induction/consolidation chemotherapy before the onset of haematopoietic stem cell transplantation (HSCT). CFU-F frequency increases from diagnosis to remission. Nevertheless level of stromal derived factor-1 (SDF-1) transcripts in bone marrow MSCs of patients with AML stays low. Considering the role of SDF-1 in the homing of HSC, the consequences of SDF-1 deficiency observed in this study might be deleterious on the engraftment after HSCT and haematopoietic recovery. The whole result of this clinical study is an argument for MSC infusion to restore a normal level of SDF1 in the bone marrow microenvironment that could reduce hematopoietic toxicity of chemotherapy and improve HSC engraftment after HSCT.
authors.forename: Loic
authors.initials: L
authors.lastname: Fouillard
authors.forename: Sabine
authors.initials: S
authors.lastname: Francois
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bouchet
authors.forename: Morad
authors.initials: M
authors.lastname: Bensidhoum
authors.forename: Abdelatif
authors.initials: A
authors.lastname: Elm'selmi
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de Radiopathologie et de Thérapie Expérimentale, BP 17, 92262 Fontenay- aux-Roses, France. alain.chapel@irsn.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
mesh_terms: D064987:Cell- and Tissue-Based Therapy; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D059248:Chemoradiotherapy / Q000009:adverse effects; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger