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
Loic Fouillard, Sabine Francois, Sandrine Bouchet, Morad Bensidhoum, Abdelatif Elm’selmi and Alain Chapel
Pages 842-848 (7)
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.
Acute myeloid leukemia, Bone marrow microenvironment, Chemo-radiotherapy, Engraftment and haematopoietic
recovery, Hematopoietic stem cells transplantation, Mesenchymal stem cells, Stromal-derived factor-1 (SDF-1).
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de Radiopathologie et de Thérapie Expérimentale, BP 17, 92262 Fontenay- aux-Roses, France.