Delineation of the human hematolymphoid system: Potential applications of defined cell populations in cellular therapy

Hematopoietic stem cells (HSC) have the capacity to reconstitute all the blood cells in the body. HSC are rare, representing on average 0.05% of the mononuclear cells present in healthy human bone marrow. Due to their capacity for self-renewal and their pluripotent, long-term reconstituting potential, HSC are considered ideal for transplantation to reconstitute the hematopoietic system after treatment for various hematologic disorders or as a target for the delivery of therapeutic genes. Human HSC also have potential applications in restoring the immune system in autoimmune diseases and in the induction of tolerance for allogeneic solid organ transplantation. With the increased interest in human HSC for clinical applications, technology for the isolation of candidate HSC and knowledge of human hematopoiesis have been growing rapidly. In this article, we discuss the functional characterization of a human CD34(+)Thy-1(+) HSC population which is essentially free of residual disease, our efforts to generate alternate monoclonal antibodies for the isolation of clinically useful stem or progenitor cell populations, and the identification of a never lymphoid progenitor as part of an exploration towards defining progenitors with potential application as adjuncts to HSC-based cellular therapy.