Mitch Biermann1 and Tannishtha Reya1,2 1Department of Medicine, University of California San Diego, La Jolla, California 92093; 2Department of Pharmacology, University of California San Diego, La Jolla, California 92093 Correspondence: mbiermannhealth.ucsd.edu; treyahealth.ucsd.edu

Hematopoietic stem cell (HSC) regeneration is the remarkable process by which extremely rare, normally inactive cells of the bone marrow can replace an entire organ if called to do so by injury or harnessed by transplantation. HSC research is arguably the first quantitative single-cell science and the foundation of adult stem cell biology. Bone marrow transplant is the oldest and most refined technique of regenerative medicine. Here we review the intertwined history of the discovery of HSCs and bone marrow transplant, the molecular and cellular mechanisms of HSC self-renewal, and the use of HSCs and their derivatives for cell therapy.