Israel Immunological Society 2025

CD74 is a Regulator of Hematopoietic Stem Cell maintenance and Expansion

Shirly Herman 1 Miri Assayag 2 Batia Avni 2 Gil Benedek 2 Arthur A Vandenbark 3 Idit Shachar 1
1Department of System Immunology, Weizmann Institute of Science
2Department of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah Medical Center
3Department of Neurology, Oregon Health & Science University

Hematopoietic stem and progenitor cells (HSPCs) are a small population of undifferentiated cells that have the capacity for self-renewal and differentiate into all blood cell lineages. These cells are the most useful cells for clinical transplantations and for regenerative medicine..
So far, it has not been possible to expand adult hematopoietic stem cells (HSCs) without losing their self-renewal properties. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF). Previously, we demonstrated that mice lacking CD74 exhibit an accumulation of HSCs in the bone marrow (BM) due to their increased potential to repopulate and compete for BM niches. Its absence leads to induced survival of these cells and accumulation of quiescent and proliferating cells. Furthermore, in in vitro experiments, blocking of CD74 elevated the numbers of HSPCs. In the current study, we examined if we could translate these findings to human patients. We investigated whether CD74-blocking is as effective in human as it is in mice. We showed that culturing ex vivo mobilized peripheral blood cells from human donors with CD74 blocker can produce a greater number of viable HSCs.
Thus, we suggest that blocking CD74 could lead to improved clinical insight into BM transplant protocols, enabling improved engraftment.