Biology of Human Umbilical Cord Blood‐Derived Hematopoietic Stem/Progenitor Cells

Abstract

Reported in 1989, studies by Broxmeyer, Gluckman, and colleagues demonstrated that umbilical cord blood (UCB) is a rich source of hematopoietic stem/progenitor cells (HSPC) and that UCB could be used in clinical settings for hematopoietic cell transplantation. Since then, a great interest has been generated on the biological characterization of these cells. Over the last nine years, several groups have focused on the study of UCB HSPC, addressing different aspects, such as the frequency of these cells in UCB, the identification of different HSPC subsets based on their immunophenotype, their ability to respond to hematopoietic cytokines, the factors that control their proliferation and expansion potentials, and their capacity to reconstitute hematopoiesis in animal models. Most of these studies have shown that significant functional differences exist between HSPC from UCB and adult bone marrow (i.e., the former possess higher proliferation and expansion potential than the latter). It is also noteworthy that genetic manipulation of UCB HSPC has been achieved by several groups and that genetically modified UCB cells have already been used in the clinic. In spite of the significant advances in the characterization of these cells, we are still in the process of trying to fully understand their biology, both at the cellular and the molecular levels. In the present article, we describe and discuss what is currently known about the biology of UCB HSPC. Stem Cells 1998;16:153-165 STEM CELLS 1998;16:153-165

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk

“…The processing of samples, which includes the determination of cord blood volumes, the determination of initial levels of total nucleated cells (TNC) and mononuclear cells (MNC) before centrifugations or manipulation, the quantitation of haematopoietic stem/progenitor cell populations and the determination of cord blood plasma hormone levels, have been described (Savarese et al, 2007). The haematopoietic stem and progenitor populations that were quantitated (1) CD34 þ cells, a heterogeneous population of early multipotent stem and progenitor cells, committed progenitors and differentiating cells (Xiao and Dooley, 2000); (2) CD34 þ CD38 À cells, which represent more primitive stem cells depleted of lineage-committed precursors (Xiao and Dooley, 2000); (3) CD34 þ c-kit þ cells, which also represent a more primitive stem cell population that has relatively high cloning efficiencies in semisolid culture (Sharkey et al, 1994;Mayani and Lansdorp, 1998); and (4) granulocytemacrophage colony forming units (CFU-GM), a functional measure of the number of proliferative granulocyte/macrophagecommitted haematopoietic precursor cells (Abboud et al, 1992;Hoffbrand et al, 2001).…”

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking Pathway

“…hMSCs have been studied extensively over the past 3 decades, and numerous independent research groups have successfully isolated hMSCs from a variety of sources, most commonly, from the bone marrow (Owen, 1988;Umezawa et al, 1992;Jaiswal et al, 1997;Makino et al, 1999;Pittenger et al, 1999;Sekiya et al, 2004). Umbilical cord blood (UCB) contains circulating stem/progenitor cells, and the cells contained in UCB are known to be distinct from those contained in bone marrow and adult peripheral blood (Mayani and Lansdorp, 1998). Isolation, characterization, and differentiation of clonally expanded hMSCs derived from UCB (UCBMSCs) have been reported (Goodwin et al, 2001;Lee et al, 2004), and UCBMSCs have been found to have multipotency, and the immunophenotype of the clonally expanded cells is consistent with that reported for bone marrow mesenchymal stem cells.…”

Determinación fenotípica de subpoblaciones de células madre derivadas de sangre de cordón umbilical.

“…Sin embargo, fue diez años más tarde que se documentó la presencia de progenitores hematopoyéticos en sangre de cordón umbilical; desde entonces, se ha incrementado el interés por el uso de la sangre de cordón umbilical como recurso alterno para obtener células madre hematopoyéticas diferentes a las de médula ósea (5). Se ha encontrado que la molécula CD34 se expresa en la mayoría de las células madre hematopoyéticas, por lo que se ha convertido en el principal marcador para su caracterización.…”

“…Estudios recientes sobre la composición bioquímica y estructural de la molécula CD34, incluido el de la secuencia de los aminoácidos y carbohidratos que la componen, han revelado que este antígeno es una molécula altamente glicosilada y acídica (punto isoeléctrico <4,0), y su peso corresponde a 110.000 daltons. Otros experimentos indican que CD34 es una fosfoproteína, puesto que los procesos relacionados con fosforilación están involucrados como un mecanismo que regula el funcionamiento de las glicoproteínas de superficie y de los receptores de los factores de crecimiento, lo cual podría dar una clave del papel del CD34 como un regulador de los procesos hematopoyéticos (2)(3)(4)(5).…”