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PhD Discussion Session: Elisabet Martí and Maria Valls
Friday, May 27, 2016 @ 10:00 am–11:00 am
Amphoteric polyamidoamines as innovative tools to selectively direct antimalarial drug towards Plasmodium-infected red blood cellsElisabet Martí, Nanomalaria joint group
Malaria, caused by the protist Plasmodium spp., in 2015 alone claimed the lives of more than 400,000 people, mainly young African children, and it had been responsible for 214 million new cases. Despite a significant decrease in the number of malaria-related deaths, there is still a need for new therapeutic strategies such as finding new antimalarial drugs or substantially improving old ones, by decreasing side effects and avoiding resistance appearance. The development of highly specific and efficient targeted nanocarriers can be the engine of this change, which however needs to be done at an affordable cost for malaria endemic countries.
Four different polyamidoamine (PAA) polymers are being studied in our group with the aim of developing a targeted nanovector capable of reaching in the mid term the preclinical pipeline.
The PAA AGMA1 had shown in previous studies antimalarial activity per se at non-toxic concentrations, as well as certain specificity for pRBCs vs. RBCs. We are trying to elucidate the corresponding mechanisms by characterizing the interaction between AGMA1 and pRBCs. Experiments such as targeting and growth inhibition assays in vitro, antimalarial activity in vivo and determination of encapsulation capacity are being currently performedwith AGMA1and with three other PAAs: ISA23, ISA1 and ARGO7. Preliminary results suggest the capacity of AGMA1 to activate the immune system, indicating that PAAs could be eventually used as an agent with double activity as a drug nanocarrier and as a prophylactic agent.
Development of a Biomimetic Bioreactor for Cardiac Tissue Engineering ApplicationsMaria Valls, Biomimetic systems for cell engineering group
Ischemic heart disease is a major cause of human death worldwide owing to the heart’s minimal ability to repair following injury. Therefore, shedding light on heart regeneration and its possible application in medicine is of paramount interest for the scientific community. In this sense, cardiac tissue engineering aims at obtaining cardiac patches for regenerative medicine purposes. In addition, these patches could serve as valuable in vitro models to study heart development and regeneration, heart diseases or as drug screening platforms.
A prerequisite for obtaining faithful cardiac patches is to mimic the native cardiac environment. Although major advances have been done, the generation of mature tissue constructs from human induced pluripotent stem (hiPS) cells is still a challenge. To address this, we have developed a parallelized perfusion bioreactor system and characterized a collagen-based 3D scaffold. Also, we have designed a perfusion chamber including graphite electrodes to electrically stimulate cells during culture. With this setup, we have obtained contractile cardiac tissue constructs from primary cultures of neonatal rat heart ventricles that show an enhanced response when cultured under electrical stimulation.
We are currently culturing cardiac progenitors derived from hiPS cells, to produce useful human cardiac tissue surrogates to study cardiovascular tissue maturation as well as for drug/toxicity testing.