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Multidisciplinary Approaches for Regenerative Medicine and Cancer Treatment from Tissue Engineering to Targeted Drug Delivery

Wednesday, March 8, 2017, 1:00 PM
ERB 228

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Pilar De La Puente Garcia, Ph.D., Postdoctoral Research Associate, Radiation Oncology, Washington University in St. Louis School of Medicine

Abstract: Tissue engineering and drug delivery are highly successful techniques of the modern biomedical engineering field. Cell behaviors within tissues are predicated upon three-dimensional (3D) interactions with extracellular matrix (ECM) and other cells, and it is clear that traditional two-dimensional (2D) culture approaches are insufficient to mimic real tissue architecture. Plasma-derived tissue engineered scaffolds have been characterized for regenerative medicine and mimicking tumor microenvironment. Mesenchymal stem cells were able to integrate, adhere, and proliferate within the biocompatible and porous network of plasma-derived scaffolds, which structure is similar to the native extracellular ECM. Furthermore, plasma-derived scaffolds allowed the differentiation of dermal cells into adipogenic, osteogenic, and chondrogenic phenotypes, overcoming pitfalls of classical differentiation methods as monolayers. Plasma-derived scaffolds were also used to develop a 3D tissue engineered bone marrow (3DTEBM) culture model made with cells from multiple myeloma (MM) patients, which allowed better evaluation of interactions of MM cells and their microenvironment and how these interactions may affect MM drug resistance. 3DTEBM recapitulated the BM microenvironment with oxygen and drug gradients, and patho-physiological cellular distribution. However, despite the great potential of tissue engineering individually, the main limiting factor for the effective use of chemotherapies in cancer is the serious side effects caused by these drugs. Novel targeted nanoparticules using CD38 as targeting moiety have been generated for specific and targeted drug delivery to MM cells. The targeted nanoparticles have shown to specifically bind to MM cells compared to normal mononuclear cells, have a preferential drug release in MM-tumor environments, improving therapeutic efficacy of the chemotherapeutic agent while reducing side effects compared to free drug. In addition, biodegradable hydrogel-implants for localized radio-chemotherapy treatment of brain tumors have been elaborated. While the hydrogels were loaded with chemotherapy directly dispersed in the hydrogel to promote immediate and localized release, the radioactive material was entrapped in microcapsules before incorporation into the hydrogel to prevent radioactivity release to the adjacent tissue and distant organs to facilitate localized radiotherapy. Localized radio-chemotherapy treatment showed improved efficacy in inhibition of tumor progression and increase overall survival in subcutaneous brain tumor models. Therefore, a combination of multidisciplinary approaches allowed investigation of stem cell biology and recreation of tumor microenvironment by capturing 3D features and cellular heterogeneity for assessment of therapeutic efficacy in cancer, as well as, control of tissue concentration and spatial drug localization, which are critical factors for safety and effectiveness of therapies.

Biography: Pilar De la Puente is a postdoctoral research associate in the Cancer Biology Division of the Department of Radiation Oncology at Washington University in St. Louis. De la Puente finished her undergraduate studies in biology at the University of Leon (2008), where continued her studies and earned her M.Sc. in biology (2010). She earned her Ph.D. degree from the University of Salamanca, focusing on tissue engineering in regenerative medicine (2012), then joined Kareem Azab’s lab at Washington University in St. Louis for her postdoctoral training. Her focus is on engineering tumor microenvironments for cancer therapy, as well as novel drug delivery devices to reduce side effects of therapies. De la Puente has co-authored more than 25 peer-reviewed papers, book chapters, and patents.

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