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

Abstract

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 novel lymphoid progenitor as part of an exploration towards defining progenitors with potential application as adjuncts to HSC-based cellular therapy.

Cloning, expression and characterization of a novel human CAP10-like gene hCLP46 from CD34+ stem/progenitor cells

“…The growth abnormalities of hematopoietic stem/progenitor cells (HSPCs) in these discorders involve a defect in the capacity of progenitor cells to respond to stimulation with growth factors. Normal HSPCs have the unique ability to undergo self-renewal and to differentiate into cells belonging to multiple hematopoietic lineages and these properties allow stem cells to maintain hematopoiesis throughout the life span of an organism (Morrison et al, 1995;Chen et al, 1997). The self-renewal capacity of several classes of stem cells is thought being controlled by external signals and intrinsic cellular processes (Morrison et al, 1995;Chen et al, 1997;Bruno et al, 1995).…”

Human CD34+ stem cells express the hiwigene, a human homologue of the Drosophila genepiwi

“…1,2 These properties allow stem cells to maintain hematopoiesis throughout the life span of an organism. The knowledge of the behavior of HSCs is limited due to their rarity, difficulty of efficient isolation, and sensitivity to manipulation.…”

“…The knowledge of the behavior of HSCs is limited due to their rarity, difficulty of efficient isolation, and sensitivity to manipulation. 1,2 The self-renewal capacity of several classes of stem cells is thought to be controlled by external signals and intrinsic cellular processes. [1][2][3][4] Over the last 2 decades, a variety of external stimuli (cytokines, matrix proteins) that alter HSC self-renewal have been the subject of intense investigation.…”

“…1,2 The self-renewal capacity of several classes of stem cells is thought to be controlled by external signals and intrinsic cellular processes. [1][2][3][4] Over the last 2 decades, a variety of external stimuli (cytokines, matrix proteins) that alter HSC self-renewal have been the subject of intense investigation. Although a number of such external signals that interact with specific receptors on HSC have been identified, the signaling mechanisms that govern HSC self-renewal have eluded investigation.…”

In Vitro Models of Human T Cell Development: Dishing Out Progenitor T Cells

“…All cells of the erythroid, myeloid, and lymphoid lineages are derived from pluripotent hematopoietic stem cells (HSCs), which typically express the sialomucin-like adhesion CD34 and lack lineage-specific markers (CD34 + Lin -) [6,7]. In the adult, most hematopoietic cells are generated in the bone marrow, which also supports in distinct niches HSC self-renewal [8,9], myelo-erythropoiesis, and B cell development [10].…”