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
Résumé
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. © 2013 Bentham Science Publishers.
Mots clés
chemotactic factor
messenger RNA
stroma derived factor 1
unclassified drug
5' nucleotidase
CD45 antigen
chemotactic factor
endoglin
stromal cell derived factor 1
Thy 1 antigen
acute granulocytic leukemia
adult
article
bone marrow biopsy
cell differentiation
cell proliferation
cell therapy
chemotherapy
clinical article
colony forming unit fibroblast
female
fibroblast
hematopoiesis
hematopoietic stem cell
hematopoietic stem cell transplantation
human
human cell
human tissue
male
mesenchymal stem cell transplantation
microenvironment
middle aged
phenotype
protein expression
real time polymerase chain reaction
acute myeloblastic leukemia
Article
bone marrow derived mesenchymal stem cell
cancer chemotherapy
cancer regression
chemoradiotherapy
colony forming unit F
controlled study
fluorescence activated cell sorting
fluorescence microscopy
gene expression
leukemia remission
Cell- and Tissue-Based Therapy
Chemokine CXCL12
Chemoradiotherapy
Hematopoiesis
Hematopoietic Stem Cell Transplantation
Humans
Leukemia
Myeloid
Acute
Mesenchymal Stromal Cells
RNA
Messenger