Biology of Hematopoietic Stem Cells and Progenitors: Implications for Clinical Application

Abstract

Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases.

Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis

“…The success of BM transplantation has provided unequivocal evidence that CD34ϩ cells isolated from the BM or circulating blood have stem cell activity (16). In the BM, CD34ϩ cells live in specialized niches, which critically determines their fate and cell cycle behavior.…”

“…Circulating BM-derived stem cells represent a small population of nucleated blood cells (15). Within the CD34ϩ population of circulating HSCs, a subpopulation expresses the vascular endothelial growth factor receptor 2 (VEGFR-2) and likely represents endothelial precursor cells that give rise to new blood vessels (16,17). VEGFR-2ϩ CD34ϩ cells have been localized in synovial tissue from RA as well as osteoarthritis patients (18), and a decreased number of endothelial precursor cells has been found in RA patients (19), suggesting that circulating progenitor cells accumulate in and feed the inflammatory lesions.…”

Regulation of FLT3 and its ligand in normal hematopoietic progenitor cells

“…Hematopoiesis is a complex process in which survival, proliferation, differentiation, and other functions are at least partially regulated through a network of growth factors [1,[31][32][33]. FLT3 and its ligand FL are known regulators in this process, mainly enhancing effects of other cytokines more than having specific effects by itself.…”

“…Expansion and regeneration of specific lineages are largely regulated by different hematopoietic cytokines [1]. Ligand-mediated activation of the FMS-like tyrosine kinase-3 (FLT3) receptor is one of the regulators of HSC self-renewal and differentiation (reviewed in [2,3]).…”

A novel role for proteomics in the discovery of cell‐surface markers on stem cells: Scratching the surface

“…For these reasons, the concept of cell-replacement or cell-supplement therapy has been advocated as a novel therapeutic approach. Importantly, treatments to replace, repair or enhance the biological function of damaged tissue or organs through celltransplantation/replacement therapy have proven successful in the case of a few syndromes, the best examples of which are bone marrow transplantations for the treatment of leukemia after myeloablative therapies, breast cancer, or congenital immunodeficiencies, and cultured epidermal autographs in the case of severe burns (reviewed in [1][2][3][4][5]). The ability to isolate, cultivate, multiply and manipulate these cells for therapeutics has, however, either limited or encouraged their use [1,2,6].…”