Which Stem Cells Should be Used for Transplantation?

Abstract

In view of the ever-increasing demand for human stem cells for transplantation, we initiated in vitro and in vivo studies of human fetal bone marrow stem/progenitor cells derived from lost pregnancies at 16–20 weeks. Utilizing non-human primates as models, we demonstrated that fetal tissue has distinctive biological and therapeutic properties that are optimal for transplantation. Subsequently, we tested and compared the phenotypic and functional characteristics of fetal bone marrow (FBM), adult bone marrow (ABM), and cord blood (CB) and peripheral blood (PB) sources of the most primitive stem/progenitor cells. A striking ontogenic difference in the proportion of CD34+ cells in FBM, ABM, PB and CB was observed (24.6 vs. 2.1 vs. 0.5 vs. 2%). The clonogenic potential, as measured by the CFU-c assay, was also higher in FBM when compared with ABM, PB and CB (202.5 vs. 73.5 vs. 40.8 vs. 65.5 colonies/10⁵cells). Moreover, there was a significant decrease in proliferative responsiveness in the mixed lymphocyte reaction (MLR) assay of FBM and CB as compared to ABM and PB. The cytokinetic profiles of the cells from the four sources were also analyzed. This study revealed that both FBM and ABM had a higher proportion of S-phase (21.7 and 11.5%, respectively), compared to PB and CB cells (1.2 and 2.8%, respectively). FBM and ABM also showed a higher proportion of cells in the G₂-M phase (6.4 and 2.6%, respectively) compared with PB and CB (1.7 and 1.2%, respectively). These data show that FBM has the highest number of proliferating cells. We have also investigated the ontogenic differences in stromal cells derived from FBM, ABM and CB, with a special focus on the expression of selected cytokines, such as CSF, GM-CSF, G-CSF, M-CSF, IL-3, IL-6, IL-10 and IL-11. FBM showed the highest levels of expression of CSF, IL-6 and IL-11 when compared to the other sources. These cytokines may have an important role in engraftment and homing of stem cells. The levels of expression of the other cytokines were similar in all sources of stromal cells, with the exception of G-CSF, which was not detected in CB. Moreover, the number of colonies FBM and ABM cells was higher when inoculated with fetal stromal cells. These results suggested an important regulatory role of cytokines in ontogeny of hematopoiesis. In summary, the foregoing observations indicate that each source of hematopoietic and stromal cells has different intrinsic properties, closely correlated with ontogenetic age, which is a vital determinant for phenotypic characteristics, lineage commitments, immunogenicity as well as proliferative potentials. Our data clearly indicate that FBM is the best source of stem cells for engraftment and therapeutic reconstitution due to its very high proliferative capacity, low immunogenicity and highest number of primitive stem/progenitor cells. It should also be stressed that FBM stem cells retrieved at their optimal stage of hematopoiesis (16–20 weeks) may be the cells of choice for both therapeutic cellular reconstitution...

Source of cell injected is a critical factors for short and long engraftment in xeno‐transplantation

“…In particular, foetal bone marrow seems to be richer in CD34 + cells compared to adult bone marrow, peripheral blood mononuclear cells and cord blood, and show very low capacity for immunoreactivity, in comparison to those other sources (Wu 1999, Michejda 2004). In addition, foetal bone marrow showed highest levels of expression of selected cytokines such as CSF, IL‐6 and IL‐11 when compared to the other sources (Michejda 2004). We can speculate that these special characteristics of foetal bone marrow are responsible for good short‐term engraftment in foetuses of the second group; on the other hand, the rapid decline in chimaerism could be related to the lack of CD3 cells.…”

“…In comparison to adult stem cells, foetal stem cells have advantages of better intrinsic homing and engraftment, greater multipotentiality and lower immunogenicity (O'Donoghue & Fisk 2004). Michejda (2004) recently reported that foetal bone marrow is the best source of stem cells for engraftment and therapeutic reconstitution, due to its high proliferative capacity, low immunogenicity and highest ration of primitive stem/progenitor cells. The aim of the present study was to investigate the possible role of the source of stem cells injected into coelomic cavities on both long‐ and short‐term engraftment.…”

Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

“…However, such interspecies experiments have been performed previously, showing that mouse-derived stromal cells could effectively support human progenitor cells [53], [54]. Additionally, cord blood cells have a relatively low immunogeneity compared to bone marrow cells [55], [56], which could have reduced the effects of interspecies differences. Moreover, these factors were all similar in the diabetic as well as in the non-diabetic experiments and therefore unlikely to have resulted in bias.…”

No evidence of clonal dominance after transplant of HOXB4-expanded cord blood cells in a nonhuman primate model

“…Exposure to stem cell factor (SCF) and interleukin 3 (IL3) significantly increase cycling in cord blood CD34 + cells but have no effect on bone marrow CD34 + cells [21]. Furthermore, in studies comparing cytokine expression levels between cord blood and bone marrow, it was found that G-CSF was not detected in cord blood [22]. Other literature has cited differences in the immunogenicity and naivety of cord blood cells [23].…”