Abstract
Due to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been widely investigated. MSCs have been proved capable of migration towards areas of inflammation, including tumors. Therefore, they have been suggested as vectors to carry therapies, specifically to neoplasias. As most of the individuals joining clinical trials that use MSCs for cancer and other pathologies are carefully recruited and do not suffer from other diseases, here we decided to study the safety and application of iv-injected MSCs in animals simultaneously induced with different inflammatory pathologies (diabetes, wound healing and tumors). We studied this by in vitro and in vivo approaches using different gene reporters (GFP, hNIS, and f-Luc) and non-invasive techniques (PET, BLI, or fluorescence). Our results found that MSCs reached different organs depending on the previously induced pathology. Moreover, we evaluated the property of MSCs to target tumors as vectors to deliver adenoviruses, including the interaction between tumor microenvironment and MSCs on their arrival. Mechanisms such as transdifferentiation, MSC fusion with cells, or paracrine processes after MSCs homing were studied, increasing the knowledge and safety of this new therapy for cancer.
Highlights
Despite the development of novel therapeutic methods in recent years, there is a lack of standard and effective therapies for pathologies such as cancer, diabetes, or stroke
As all of our reporter genes were inserted in adenoviral vectors, first, we evaluated the ability of mesenchymal stem cells (MSCs) to be productively infected by those vectors, expressing our reporter genes
We found that labeled MSCs can migrate to and survive in tumor xenografts, pancreas, and skin by different approaches
Summary
Despite the development of novel therapeutic methods in recent years, there is a lack of standard and effective therapies for pathologies such as cancer, diabetes, or stroke. This represents a major challenge for public health in all countries. The scientific community has focused its efforts on developing advanced therapies, such as gene and cell therapies. Advanced therapies are designed to increase tissue selectivity to avoid the immune response, and to reach high expression levels of the therapeutic gene included in the vector at the area of interest. The development of new vectors is essential for the improvement/progression of gene therapy
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