Therapeutic effect of human adipose-derived stem cells and their secretome in experimental diabetic pain.

Painful neuropathy is one of the complications of diabetes mellitus that adversely affects patients'quality of life. Pharmacological treatments are not fully satisfactory, and novel approaches needed. In a preclinical mouse model of diabetes the effect of both human mesenchymal stromal cells from adipose tissue (hASC) and their conditioned medium (hASC-CM) was evaluated. Diabetes was induced by streptozotocin. After neuropathic hypersensitivity was established, mice were intravenously injected with either 1 × 106 hASC or with CM derived from 2 × 106 hASC. Both hASC and CM (secretome) reversed mechanical, thermal allodynia and thermal hyperalgesia, with a rapid and long lasting effect, maintained up to 12 weeks after treatments. In nerves, dorsal root ganglia and spinal cord of neuropathic mice we determined high IL-1ß, IL-6 and TNF-α and low IL-10 levels. Both treatments restored a correct pro/antinflammatory cytokine balance and prevented skin innervation loss. In spleens of streptozotocin-mice, both hASC and hASC-CM re-established Th1/Th2 balance that was shifted to Th1 during diabetes. Blood glucose levels were unaffected although diabetic animals regained weight, and kidney morphology was recovered by treatments. Our data show that hASC and hASC-CM treatments may be promising approaches for diabetic neuropathic pain, and suggest that cell effect is likely mediated by their secretome.

Cutting Edge: IgE Plays an Active Role in Tumor Immunosurveillance in Mice.

Exogenous IgE acts as an adjuvant in tumor vaccination in mice, and therefore a direct role of endogenous IgE in tumor immunosurveillance was investigated. By using genetically engineered mice, we found that IgE ablation rendered mice more susceptible to the growth of transplantable tumors. Conversely, a strengthened IgE response provided mice with partial or complete resistance to tumor growth, depending on the tumor type. By genetic crosses, we showed that IgE-mediated tumor protection was mostly lost in mice lacking FcεRI. Tumor protection was also lost after depletion of CD8(+) T cells, highlighting a cross-talk between IgE and T cell-mediated tumor immunosurveillance. Our findings provide the rationale for clinical observations that relate atopy with a lower risk for developing cancer and open new avenues for the design of immunotherapeutics relevant for clinical oncology.

Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel.

OBJECTIVE: Gingival tissue is composed of cell types that contribute to the body's defense against many agents in oral environment, wound healing and tissue regeneration. Thanks to their easy and scarcely invasive withdrawal procedure, interdental papilla provide a good source of mesenchymal stromal cells (GinPa-MSCs). We isolated GinPa-MSCs and verified their ability to uptake/release the anticancer agent Paclitaxel (PTX). METHODS: In vitro expanded GinPa-MSCs were characterized for CD markers by FACS, tested for differentiation ability and analyzed by TEM. Their ability to uptake/release PTX was assessed according to a standardized procedure. RESULTS: The CD expression and chondro-adipo-osteo differentiation ability confirmed the mesenchymal feature of GinPa-MSCs. Surprisingly, 28% of GinPa-MSCs expressed CD14 marker and had an impressive pinocytotic activity. GinPa-MSCs were able to take up and release a sufficient amount of PTX to demonstrate effective in vitro activity against pancreatic carcinoma cells, suggesting that the drug was not inactivated. CONCLUSIONS: The procedure to obtain MSCs from interdental papilla is less invasive than that used for both bone marrow and adipose tissue, GinPa-MSCs are easy to expand and can be efficiently loaded with PTX. Taken together these qualities suggest that GinPa-MSCs may prove to be a good tool for cell-mediated drug delivery in cancer, particularly if related to stomatognathic system.