There is no transfer of mitochondria from donor hematopoietic cells to recipient mesenchymal stromal cells after allogeneic hematopoietic stem cells transplantation in humans

Abstract

Introduction

Multipotent mesenchymal stromal cells are progenitors of the bone marrow stromal microenvironment that support hematopoiesis. Mitochondria, which can be transferred between cells via nanotubes or extracellular vesicles, play a key role in the functions of mesenchymal stromal cells. In a murine model, donor hematopoietic stem and progenitor cells transfer functional mitochondria to bone marrow mesenchymal stromal cells of the recipient. The aim of this study was to find out whether such transfer occurs in humans after allogeneic hematopoietic stem cell transplantation.

Methods

This study included nine patients with acute leukemia who received a reduced intensity conditioning regimen. Donor hematopoietic stem and progenitor cells mobilized into peripheral blood were the source of transplanted stem cells. Total DNA was isolated from bone marrow mesenchymal stromal cells of each patient before and after transplantation and their respective donors’ leukocytes. A fragment of mitochondrial DNA including the full-length control region was sequenced. The mitochondrial DNA sequence of each patient’s mesenchymal stromal cells was compared before and after the procedure and with the respective donor leukocytes.

Results

Donor mitochondrial DNA was not detected in the mesenchymal stromal cells of any patient after transplantation even as trace amounts. Co-culturing donor leukocytes with intact and irradiated mesenchymal stromal cells in vitro did not lead to detection of donor mitochondrial DNA transfer.

Conclusion

The data show that there is no mitochondrial transfer from donor hematopoietic stem and progenitor cells to recipient mesenchymal stromal cells after transplantation. Thus, the results indicate that one cannot count on improved mesenchymal stromal cell metabolism due to mitochondrial transfer. It is necessary to look for other ways to restore the stromal microenvironment.