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.

Leukemia stem cells promote chemoresistance by inducing downregulation of lumican in mesenchymal stem cells

“…These findings are consistent with the results of the present study. In accordance with previous studies (23)(24)(25)(26)(27)(28), the results of the present study demonstrated reduced SDF-1 and IL-6 levels, and increased IL-10, G-CSF, IL-3, IL-7, SCF, IL-11, IL-1α, IL-1β and LIF levels after LSC-BM-MSCs co-culture for 24-72 h.…”

Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation

“…In MMSCs derived from ALL BM, stable downregulation of SDF1 was detected. A similar effect has also been described in patients with AML, [46] but it was not detected in our study. SDF1 is a well-known stromal chemokine regulating the homing of hematopoietic stem cells to the BM niches.…”

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…MSCs are part of this niche and secrete a number of haematopoietic growth factors. To facilitate the engraftment of haematopoietic stem cells and stimulate blood formation, the MSCs should successfully home to and persist in the bone marrow [31] . In this review, we discuss current knowledge about MSC homing, specifically focusing on bone marrow homing (based on both in vitro and in vivo data), and we review the efforts that different groups have undertaken to improve the homing efficiency of these cells.…”