Ex vivo allogeneic stimulation significantly improves expansion of cytokine-induced killer cells without increasing their alloreactivity across HLA barriers.

Cytokine-induced killer cells (CIKs) are ex vivo expanded T-NK lymphocytes capable of HLA-unrestricted antitumor activity. CIKs are promising candidates for adoptive cancer immunotherapies; they can be generated and infused in autologous settings of cancer patients, or from donors, after allogeneic hematopoietic cell transplant. Ex vivo expansion rates of CIKs are greatly variable among patients, with consequent potential clinical limitations for "poor expanders.

Transient proteasome inhibition as a strategy to enhance lentiviral transduction of hematopoietic CD34(+) cells and T lymphocytes: implications for the use of low viral doses and large-size vectors.

The proteasome system restricts lentiviral transduction of stem cells. We exploited proteasome inhibition as a strategy to enhance transduction of both hematopoietic stem cells (HSC) and T lymphocytes with low dose or large-size lentiviral vectors (LV). HSC showed higher transduction efficiency if transiently exposed to proteasome inhibitor MG132 (41.

Blood-forming stem cells are nervous: direct and indirect regulation of immature human CD34+ cells by the nervous system.

The nervous system regulates immunity through hormonal and neuronal routes as part of host defense and repair mechanism. Here, we review the emerging evidence for regulation of human hematopoietic stem and progenitor cells (HSPC) by the nervous system both directly and indirectly via their bone marrow (BM) niche-supporting stromal cells. Functional expression of several neurotransmitter receptors was demonstrated on HSPC, mainly on the more primitive CD34(+)/CD38(-/low) fraction.

Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers.

Donor-derived cytokine-induced killer (CIK) can be infused as adoptive immunotherapy after hematopoietic cell transplant (HCT). Promising results were recently reported in HLA-identical HCT, where mild grafts versus host (GVH) events were observed. To extend this strategy across major HLA barriers (e.

Sustained long-term engraftment and transgene expression of peripheral blood CD34+ cells transduced with third-generation lentiviral vectors.

As mobilized peripheral blood (MPB) represents an attractive cell source for gene therapy, we investigated the ability of third-generation lentiviral vectors (LVs) to transfer the enhanced green fluorescent protein gene into MPB CD34(+) cells in culture conditions allowing expansion of transplantable human hematopoietic stem cells. To date, few studies have reported transduction of MPB cells with vesicular stomatitis virus G pseudotyped LVs. The critical issue remains whether primitive, hematopoietic repopulating cells have, indeed, been transduced.

Vasculogenic potential of long term repopulating cord blood progenitors.

In the adult, involvement of bone marrow-derived circulating endothelial progenitor cells (EPCs) in tissue revascularization (vasculogenesis) and the cooperation of hematopoietic cell subsets in supporting this process have been described in different experimental animal models. However, the effective contribution of such cells in restoring organ vascularization in a clinical setting needs to be clarified. In this study, a mouse transplantation model was engrafted by human cord blood hematopoietic stem and progenitor cells to follow the behavior of donor-derived endothelial and hematopoietic cells in the presence of a localized source of an angiogenic inducer.