Interaction of Mesenchymal Stem/Stromal Cells with Immune Populations: Immunomodulation through Mitochondrial Transfer in the context of Allo-HSCT for patients with malignant hematological disorders
PEROUF R. 1, EL OUAFY M. 1, POCHON C. 1,2, CHARIF N. 1, GUELTON A. 1, D'AVENI-PINEY M. 1,2, RUBIO M. 1,2, DE ISLA N. 1
1 IMoPA UMR 7365 CNRS, Vandoeuvre-Lès-Nancy, France; 2 Université de Lorraine, CHRU Nancy Brabois Département d’Hématologie, Nancy, France , Vandoeuvre-Lès-Nancy , France
Oral Presentation or Poster
Malignant hematological disorders are characterized by abnormal proliferation of blasts within the hematopoietic niche, resulting in a deficiency of blood and immune cells. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment after chemotherapy to achieve remission. The bone marrow microenvironment plays a crucial role in the success of this therapy. Numerous studies have highlighted the significance of interactions between hematopoietic cells and mesenchymal stromal cells (MSCs). Recently, mitochondrial transfer from MSCs to leukemic blasts, promoting their survival during therapeutic intervention, have been highlighted. In this study, we focused on mitochondria transfer between MSCs and immune cells of the hematopoietic niche, such as T lymphocytes, dendritic cells, and iNKT cells. We could produce bone marrow-derived MSCs from leukemic patients when they were in complete remission, before allo-HSCT, and explored their senescence status and capacities to transfer mitochondria to immune cells from healthy donors. Our findings demonstrate that MSCs can transfer mitochondria to T, iNKT and DCs. In particular, we have shown that mitochondrial transfer could impact T cell metabolism and was associated with reduce T cell proliferation in vitro. Additionally, we have shown that patient-derived MSCs mitochondrial transfer to such immune populations is inversely correlated to the level of MSCs’ senescence. Furthermore, we have characterized mitochondrial dysfunction associated with the MSC senescence state as a factor regulating the capacity of MSCs to transfer mitochondria. Correlations with post-transplant outcomes, suggest that the degree of MSCs senescence can influence bone marrow microenvironment inflammatory status and correlates with the risk of disease relapse or the occurrence of graft-versus-host disease. Our results highlight the potential interest of modulating MSCs’ metabolism and senescence to influence the transfer of mitochondria to immune populations to prevent relapse or graft-versus-host disease after allo-HSCT.