Hematopoietic Capability of CD34+ Cord Blood Cells: A Comparison With CD34+ Adult Bone Marrow Cells

Abstract

The characteristics of hematopoietic progenitor and stem cell (HPC/HSC) populations in mammals vary according to their ontogenic stage. In humans, HPC/HSCs from umbilical cord blood (CB) are increasingly used as an alternative to HPC/HSCs from adult bone marrow (BM) for the treatment of various hematologic disorders. How the hematopoietic activity of progenitor and stem cells in CB differs from that in adult BM remains unclear, however. We compared CD34+ cells, a hematopoietic cell population, in CB with those in adult BM using phenotypic subpopulations analyzed by flow cytometry, the colony-forming activity in methylcellulose clonal cultures, and the repopulating ability of these cells in NOD/Shi-scid (NOD/SCID) mice. Although the proportion of CD34+ cells was higher in adult BM than in CB mononuclear cells, the more immature subpopulations, CD34+ CD33- and CD34+ CD38- cells, were present in higher proportions in CD34+ CB cells. Clonal culture assay showed that more multipotential progenitors were present in CD34+ CB cells. When transplanted into NOD/SCID mice. CD34+ adult BM cells could not reconstitute human hematopoiesis in recipient BM, but CD34+ CB cells achieved a high level of engraftment, indicating that CD34+ CB cells possess a greater repopulating ability. These results demonstrated that human hematopoiesis changes with development from fetus to adult. Furthermore, CD34+ CB cells contained a greater number of primitive hematopoietic cells, including HSCs, than did adult BM, suggesting the usefulness of CD34+ CB cells not only as a graft for therapeutic HSC transplantation but also as a target cell population for ex vivo expansion of transplantable HSCs and for gene transfer in gene therapy.

Myoendothelial Differentiation of Human Umbilical Cord Blood–Derived Stem Cells in Ischemic Limb Tissues

“…In fact, it has been reported that human EPCs derived from peripheral blood CD34 ϩ cells 50 and that UCB CD34 ϩ cell fraction contains a higher number of primitive hematopoietic cells compared with human bone marrow. 51 In our analysis, we attempted at deriving human myogenic cells by using conditioned media by both proliferating and differentiating myoblasts (not shown). Thus far, in agreement with results described by Asakura et al, 31 we could not derive any myogenic cells either by using liquid culture or semisolid culture in methylcellulose even in the presence of myoblast conditioned medium.…”

Ex vivo expansion of human hematopoietic stem and progenitor cells

“…5 In addition, CB is an increasingly utilized source of HSCs for hematopoietic cell transplantation (HCT), primarily because of its ready availability and suitability for recipients, especially minority and mixed-race individuals, who cannot identify other HLA-matched marrow or mPBSC donors. However, the limiting cell doses provided in a single CB unit have been associated with delayed hematopoietic recovery of both neutrophils and platelets.…”

Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/ 2-microglobulin-/- repopulating mobilized human peripheral blood CD34+ cells

“…However, it is of note that in previously published gene marking studies, the level of engraftment and transduction efficiency of CD34 ϩ PBSCs in the NOD/SCID model is lower compared with bone marrow (BM) or cord blood CD34 ϩ cells. [12][13][14][15] In our current study we also examine one potential basis for the performance of RD114-pseudotyped vectors by demonstrating for the first time high levels of RDR expression on hematopoietic stem cells with primitive CD34 ϩ CD38 Ϫ phenotype. Finally, we used RD114-MFGS vector encoding cyan fluorescent protein (CFP) to transduce normal CD34 ϩ PBSCs to explore the effect on the outcome of transplantation into NOD/SCID mice of prolongation of ex vivo culture to allow time for additional transductions.…”