Integration of Parallel Synthesis, Compound Management and Screening in Support to the Italian National Chemical Collection Center



August 22, 2012

Alberto Bresciani, Head, IRBM Science Park

Stem cells (SC) are capable of homing to sites of inflammation and ischemia following intravascular injection, but are often limited by inefficient tropism to pathological sites. Pulse focused ultrasound (pFUS) is a noninvasive modality that creates non-destructive non-thermal effects that increases tissue permeability and enhance delivery of drugs or genes within the treated region through the process of mechanotransduction (i.e. tissue cytokines and growth factors expression in response to mechanical force). We have shown that pFUS exposures induced local expression of chemoattractants and integrins, demonstrating the utility of pFUS to enhance homing, permeability, and retention (EHPR) of cells in vivo (PLoS ONE 2011;6:e24730). Based on our initial observations, we have tested several hypotheses to determine if pFUS will cause EHPR of SC in pathologies. Experimental studies performed in limb ischemia and acute tubular necrosis models using combining SC with pFUS to determine the effect on pathology at various time points following insult. Radiological and histological correlation was performed to determine effect of coupling pFUS with SC along with molecular analysis of tissue response to the combination therapy. These results are readily translatable to the clinic since image guided pFUS has already been approved for use in treatment of pathologies.

Drug Discovery

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