Human cord blood CD133+ cells immunoselected by a clinical‐grade apparatus differentiate in vitro into endothelial‐ and cardiomyocyte‐like cells

Abstract

The appearance of both endothelial- and cardiomyocyte-like cells from parallel cultures of frozen-thawed-immunoselected UCB CD133+ cells by a clinical-grade method and previously reported data on lack of major signs of rejection of these cells in immunocompetent rats subjected to experimental liver damage suggest a possible role of these allogeneic HSCs in cell therapies designed for regenerative treatments of ischemic diseases of human myocardium.

Development of Serum-Free Quality and Quantity Control Culture of Colony-Forming Endothelial Progenitor Cell for Vasculogenesis

“…1B, 1C). Of interest, Comb 4 exhibited greater EPC-CFU productivity, especially in DEPC-CFU, compared with the previously reported Comb 1 (SCF, Flt-3 ligand, IL-3, IL-6) for EPC expansion [5,40]. Collectively, we determined that the Comb 4 growth factors are the most effective culture system for vasculogenic colony-forming EPC expansion, and we named them the QQc control system.…”

“…Park et al reported that CB-CD133 ϩ cells cocultured with rat CMCs after pretreatment with platelet-derived growth factor and epidermal growth factor feature cardiomyocytic phenotypes in terms of morphology and expression of lineage-specific markers [48]. Bonanno et al [40] also demonstrated that a specific differentiation culture system after preconditioning of CB-CD133 ϩ cells with SCF, Flt-3 ligand, IL-3, and IL-6 for 2 days promoted differentiation into EC or CMC lineages in vitro.…”

“…On the basis of these ex vivo hematopoietic expansion cultures, the development of EPC expansion culture has also been attempted, because EPCs share common surface markers, such as CD34 and CD133, with hematopoietic stem cells. First of all, Pesce et al [5] expanded CB-CD34 ϩ cells for 7 days using a serum-free cytokine cocktail of SCF, Flt-3 ligand, interleukin-3 (IL-3), and IL-6, which was also used by Bonanno et al [40], included as Comb 1 (Table 1), and successfully increased the number of CB-CD34 ϩ cells by 10-fold. Although the arteriole length density in ischemic adductor muscles was significantly greater following transplantation of CB-CD34…”

“…Given this finding, we investigated the productivities of EPC-CFU in the several combinations, including the previously reported ones [5,40], in comparison with the combination (VEGF, SCF, TPO, Flt-3 ligand, IL-6) named Comb 4. For example, Comb 6 (SCF, TPO, Flt-3 ligand, IL-3, IL-6, VEGF) represented the most increase in cell number after culture but resulted in a significantly lower frequency of DEPC-CFU, whereas Comb 4 demonstrated the highest total EPC-CFU frequency and, in particular, the highest DEPC-CFU frequency postculture among the groups (Fig.…”

Somatic Cell Dedifferentiation/Reprogramming for Regenerative Medicine

“…Many latest researches carried out with in vitro or ex vivo differentiated ES cells, fetal and umbilical cord blood (UCB)-derived stem cells and their functional progeny as well as adult stem/progenitor cells have provided accruing substantiation sustaining their potential therapeutic application for numerous genetic and degenerative disorders (3,4,14,22,(26)(27)(28)(29)(30)(31)(32)(33). Allogenic transplantation of stem cells or their additional differentiated progeny into patients may markedly represent a potential therapeutic approach, unaccompanied or in combination with the predictable treatments, for conquering the progressive failure of functions of adult stem cells with aging and degenerative diseases (14,34).…”