Human Hematopoietic Stem Cells: Concepts and Perspectives on the Biology and Use of Fresh Versus In Vitro–Generated Cells for Therapeutic Applications

Abstract

The in vitro production of human hematopoietic stem cells (hHSCs) has caused great interest due to its clinical impact. The main goal of the present article is to review the information existing today on the in vitro generation of hHSCs and their molecular and functional integrity as compared with fresh hHSCs. By using different in vitro systems, hHSCs have been generated from fresh hHSCs (obtained from bone marrow, peripheral blood, or cord blood) and from pluripotent stem cells. Although functional and molecular gaps have been observed between fresh and in vitro–derived hHSCs, recent clinical trials indicate that hHSCs generated in vitro from cord blood are capable of long-term hematopoietic reconstitution in transplanted patients. To date, no data exist on the clinical use of hHSCs derived from human pluripotent stem cells (hPSCs). Significant achievements in hHSC expansion and manipulation, as well as in the culture and differentiation of hPSCs, have been reported. All this, together with innovative clinical trials for the treatment of hematologic disorders, will be fundamental for the in vitro generation of hHSCs and their application in clinical settings.