A method of generating hematopoietic stem cells for transplantation is disclosed. The method comprising: (a) collecting hematopoietic stem cells; and (b) contacting the hematopoietic stem cells with an agent capable of decreasing an activity or expression of CD74 and/or of macrophage migration inhibitory factor (MIF), to thereby generate hematopoietic stem cells for transplantation, and wherein the hematopoietic stem cells are not transduced with a lentivirus. Methods of increasing mobilization of hematopoietic stem cells and methods of treatment are also provided.