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San Diego, CA, United States

Marleau A.M.,Institute of Molecular Medicine | Mcdonald G.,McDonald Animal Hospital | Koropatnick J.,Lawson Health Research Institute | Koropatnick J.,University of Western Ontario | And 2 more authors.
Anticancer Research | Year: 2012

The influence of adult stem cells on tumor growth is paradoxical. On one hand, angiogenic factors secreted by stem cells are known to be essential for tumor vascularization. On the other hand, stem cell-derived factors can reportedly induce tumor differentiation or direct death of tumor cells. Both the placenta and umbilical cord are rich sources of stem cells with immune modulatory and tissue-healing properties; however, the effects of placental components on cancer cells have not been fully defined. Here we demonstrate that extracts of placental lysates reduce the malignancy of a variety of human tumor cell lines in a species-unrestricted manner. Using a standard model of leukemia cell differentiation, we demonstrated that addition of placental extracts to tumor cells, or co-culture of tumor cells with the CD34 + cells from umbilical cord blood, induced tumor cell differentiation. Inhibition of tumor growth and metastasis in vivo was also observed following administration of placental extracts. These data support the concept of non-toxic biological therapy of cancer using stem cell derivatives, possibly through the induction of tumor cell differentiation.

Zheng X.,University of Western Ontario | Popov I.,University of Western Ontario | Zhang X.,University of Western Ontario | Wang H.,Nanchang University | And 10 more authors.
Journal of Translational Medicine | Year: 2012

Background: We have previously demonstrated that immune modulation can be accomplished by administration of gene silenced dendritic cells (DC) using siRNA. In this study, we demonstrate the therapeutic utilization of shRNA-modified DC as an antigen-specific tolerogenic vaccine strategy for autoimmune arthritis.Methods: A shRNA that specifically targets IL-12 p35 was designed and cloned into a plasmid vectors (IL-12 shRNA). Bone marrow-derived DC from DBA/1 mice were transfected with the IL-12 shRNA construct in vitro. Mice with collagen II (CII)-induced arthritis (CIA) were treated with the modified DCs expressing the shRNA. Recall response and disease progression were assessed.Results: After gene silencing of IL-12 in DC, DC were shown to selectively inhibit T cell proliferation on recall responses and in an MLR. In murine CIA, we demonstrated that administration of IL-12 shRNA-expressing DC that were pulsed with CII inhibited progression of arthritis. The therapeutic effects were evidenced by decreased clinical scores, inhibition of inflammatory cell infiltration in the joint, and suppression of T cell and B cell responses to CII.Conclusion: We demonstrate a novel tolerance-inducing protocol for the treatment of autoimmune inflammatory joint disease in which the target antigen is known, utilizing DNA-directed RNA interference. © 2012 Li et al; licensee BioMed Central Ltd.

Lin F.,Entest BioMedical | Josephs S.F.,Entest BioMedical | Alexandrescu D.T.,Georgetown Dermatology | Ramos F.,Entest BioMedical | And 7 more authors.
Journal of Translational Medicine | Year: 2010

The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.© 2010 Lin et al; licensee BioMed Central Ltd.

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