bims-mithem 2025-11-23 papers

Issue of 2025–11–23
three papers selected by
Tim van Tienhoven, Erasmus Medical Center

Int Rev Immunol. 2025 Nov 17. 1-30

Mitochondria in the immune system: Therapeutic potential from mitochondria transfer.

Thao Hoang Nhu Le, Van Thi Tuong Nguyen.

Mitochondria serve as the powerhouses of living cells, supplying energy and essential building blocks for cellular activities. The immune system exhibits a dynamic and active characteristic within the body, wherein immune cells are constantly activated and primed for pathogens without causing harmful effects on the self-body. These characteristics necessitate that immune cells function effectively and correctly, supported by a sufficient energy supply and metabolism from the mitochondria. Mitochondrial dysfunction leads to immune dysregulation, resulting in inappropriate inflammation, autoimmunity, immunodeficiency, and hypersensitive responses, all of which contribute to the development of illness and disease. Recent studies on mitochondrial transfer in immune cells indicate that mitochondrial replacement could emerge as a promising tool for rectifying immune cell function. This review will emphasize the role of mitochondria in various immune cell types and explore how mitochondrial dysfunction can result in pathogenesis in different conditions. We also discuss the potential application of mitochondrial transfer and transplantation to- and from immune cells in the context of health and disease.

Keywords: Immunology; immunometabolism; mesenchymal stem cells; metabolism; mitochondria transfer

DOI: https://doi.org/10.1080/08830185.2025.2577986

Stem Cells Transl Med. 2025 Nov 14. pii: szaf061. [Epub ahead of print]14(11):

Functional and molecular analyses reveal impaired HSPCs in Multiple Myeloma patients post-induction.

Thanh Mai Baumhardt, Amanda Amoah, Markus Hoenicka, Andreas Liebold, Vadim Sakk, Karin Soller, Angelika Vollmer, Miriam Kull, Jan Kronke, Jan-Philipp Mallm, Hartmut Geiger, Medhanie Mulaw.

High-dose chemotherapy and consecutive autologous stem cell transplantation (ASCT) remain the backbone of treatment for transplant-eligible patients of Multiple Myeloma (MM). However, patients are still at high risk of relapse or treatment-related complications. Hence, by understanding the function of hematopoietic stem and progenitor cells (HSPCs) from MM patients in more detail, transplant outcomes in MM patients might be further improved. We combine in our study functional analyses of the potential of HSPCs from newly diagnosed (NDMM) and chemotherapy treated MM patients in a xenotransplant model system with in depth single cells sequencing analysis to provide novel data that might inform clinical routine to improve the outcome of ASCT in MM. Our data demonstrate that (i) HSPCs from treated MM patients are indeed significantly impaired in their overall reconstitution potential and provide a reduced level of B-cells in comparison to HSPCs from age-matched healthy donors and NDMM patients. (ii) We further demonstrate that CD34+ HSPCs acquire a high-risk MM expression profile signature upon induction treatment, which likely adds to the risk of relapse. This high-risk MM expression profile signature relies within CD34+ HSPCs primarily in granulocyte/macrophage progenitors (GMPs), megakaryocyte Erythroid Progenitors (MEPs) and monocytes, while hematopoietic stem cells (HSCs) stay unaffected by transcriptional changes. These data suggest that the elimination of myeloid progenitors and more mature monocytes (likely by purification for HSCs) in HSPCs harvests from treated MM patients for subsequent ASCT might improve transplant outcomes by avoiding re-infusion of cells with a dysregulated and disease-linked transcriptional program.

Keywords: autologous stem cell transplantation; hematopoietic stem cells; multiple myeloma; single cells sequencing; xenotransplant model

DOI: https://doi.org/10.1093/stcltm/szaf061

Nat Commun. 2025 Nov 18. 16(1): 10042

Inflammatory stromal and T cells mediate human bone marrow niche remodeling in clonal hematopoiesis and myelodysplasia.

Somatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP) and progression to myelodysplastic syndromes (MDS). Using single-cell and anatomical profiling of a large cohort of human bone marrow (BM), we show that the HSPC BM niche in CHIP and MDS is undergoing inflammatory remodeling. This includes loss of CXCL12⁺ adipogenic stromal cells and the emergence of a distinct population of inflammatory mesenchymal stromal cells (iMSCs), which arise in CHIP and become more prevalent in MDS. Functional studies in primary BM HSPC-MSC co-cultures reveals that healthy aged and CHIP HSPCs activate stromal support, while MDS HSPCs fail to do so. In contrast, MDS blasts further suppress HSPC support and trigger inflammation, indicating disease-stage-specific stromal disruption. In parallel, we show that iMSCs retain partial support and angiogenic potential in MDS, coinciding with expanded BM vasculature. Additionally, we identify IFN-responsive T cells that preferentially interact with iMSCs, potentially reinforcing local inflammation. These findings position iMSCs as central mediators of early BM niche dysfunction and potential therapeutic targets for intercepting pre-malignant hematopoiesis.

DOI: https://doi.org/10.1038/s41467-025-65803-y