A Review of the Work of More of Last Year's Class of SENS Research Foundation Interns

Young researchers intern each year at the SENS Research Foundation, doing their part to help advance the state of the art closer towards working rejuvenation treatments. The Foundation exists not just to coordinate and fund cutting edge research today, but also to help build the research community of tomorrow. Completing clinical deployment of the first generation of applied rejuvenation biotechnologies will be a big job, something that ideally will see the growth of a research community to rival the stem cell and cancer institutions in size, funding, and enthusiasm. Among today's life science undergraduates and graduates are those who will be leading laboratories two decades from now, creating therapies to reverse some of the causes of aging. But they haven't yet chosen that path, or made the necessary connections, or decided that they find the molecular biology of aging to be an exciting field, wide open for ambitious newcomers to make a mark.

If you look back in the Fight Aging! archives you'll find a few posts covering the SENS Research Foundation publications on their intern program:

This is another post in the series, looking at the more of the work accomplished by last year's class. A number of articles have been published over the last month by the Foundation, and here they are:

Search begins for non-toxic enzymatic solution to macular degeneration: 2013 intern Anuj Kudva

Age-related macular degeneration (AMD) is a major cause of sight loss in the elderly. There are multiple risk factors that can result in the onset of AMD, but it is believed that the pathogenesis of AMD is due to dysfunctional retinal pigment epithelium (RPE) cells. It is believed that the buildup of a lipofuscin molecule called A2E within RPE lysosomes hinders the metabolic behavior of RPE cells and hence causes the AMD pathogenesis. Fortunately, a recent study has provided evidence that peroxidase enzymes can metabolize A2E within lysosomes. Unfortunately 10% of the cells died as a result of the enzymatic reaction.

The goal of my research team is to identify a peroxidase enzyme that can degrade the buildup of A2E with limited toxic side effects. My project focused on developing an assay to assess the cytotoxicity of possible peroxidase enzyme treatments. We decided to measure apoptosis as a readout of cytotoxicity. I tested a number of DNA damaging agents to establish a positive control for apoptosis. With a positive control established, I began Western blot analysis of the lysate from cells treated with or without a candidate peroxidase enzyme called SENS20. I found that SENS20 has no toxic effects at concentrations up to 100 ug. Once the team overcomes a few remaining technical issues, the assay will be ready for routine use. The apoptosis assay paves the way for more conclusive cytotoxicity studies in the future.

Generation of thymus ex vivo - SRF and WFIRM intern Daniel Bullock

The thymus is an essential component of the immune system, which configures T-cells to meet novel threats. Unlike most organs, the thymus reaches its maximum size and functionality around the onset of puberty after which it atrophies, leading to a decline in the immune system's ability to respond to new threats. If it were possible to prolong the viability of the thymus, or even revitalize it later in life, we might be able to bolster the body's defences against threats such as viruses, autoimmune diseases, and even cancer.

Our goal was to develop a method for growing a transplantable thymus, using donor thymus cells to colonize a scaffold containing an extracellular matrix, the mesh of tissue components found between cells. This entailed a number of intermediary steps, including harvesting thymic tissue from porcine donors, the decellularization of those tissues (i.e. reducing the tissue to an extracellular matrix), the harvesting of epithelial cells from murine donors, and finally the culturing of potential donor thymus tissue. Although these procedures have been successfully implemented in the past for a number of other organs and tissues, the precise protocols are only partly applicable for work with the thymus. Thus, a new protocol needed to be developed and optimized.

I performed a number of quantitative assessments to measure the optimization of the decellularization process and growth of thymic epithelial cell populations in vitro. Additionally, I also characterized the microphysical and biological features of the newly decellularized material. Our initial results have been promising and, as my internship was coming to a close, the lab was preparing to begin transplantation experiments in a live mouse model.

Stem cell-based therapy for the treatment of inflammatory bowel disease (IBD) - SRF intern John Moon

Inflammatory bowel disease is characterized by intestinal inflammation, which causes severe damage to the tissue of the intestinal lining. The precise cause of IBD remains uncertain. However, evidence suggests that dysregulation of the immune system plays a role in the autoimmune response that leads to the inflammation that characterizes IBD.

Mesenchymal stromal cells (or MSCs) are cells which differentiate into multiple tissue types and have been shown to reduce local inflammation, decrease the immune response, and counteract the signals released to recruit immune cells to the site of inflammation. It was therefore hypothesized that MSCs may be an effective therapy for IBD. However, clinical trials have demonstrated that MSC infusions were only effective in 30% of IBD patients. Furthermore, animal model studies have demonstrated that the limited tendency of MSCs to graft to the intestine may have been the limiting factor.

Previous work by the Almeida-Porada lab indicates that endothelial progenitor cells home promptly to the intestine. Therefore, my summer project sought to explore whether a cell-based therapy using a combination of both MSCs and endothelial cells (EC) would be an effective treatment for IBD.

Therefore, I isolated and characterized mesenchymal stromal cells and endothelial cells from human umbilical cord tissue. Then, I utilized flow cytometry and immunofluorescent double-staining to characterize these cells, and show that our cells are expressing molecules necessary for homing and immunomodulation. These results also lay the groundwork for future experiments to evaluate the effectiveness of cord tissue-derived MSC and EC cell therapy.


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