Abstract: Stem cell therapy has gained much interest in regenerative engineering. The regenerative potential of stem cells comes from two main mechanisms: 1) multipotent ability to differentiate into multiple cell lineages and replace injured tissue and 2) secretion of bioactive factors to signal regenerative processes in surrounding cells. However, stem cell therapy faces limitations such as limited availability and spontaneous phenotypic and genetic changes during expansion. The paracrine action of stem cells has been attributed as one of the major contributing factor to regeneration, though the composition of the secretome is highly dynamic and dependent on the cell’s microenvironment. This dissertation evaluates the feasibility of a synthetic artificial stem cell. The goal is to harness the paracrine action of stem cells, capable of controlled release of a tailored secretome factors at the site of injury. Osteoarthritis, a highly prevalent degenerative disease characterized by inflammation followed by subsequent matrix degeneration, is used as a disease model. In an in vitro co-culture model with inflamed chondrocytes, the anti-inflammatory and chondro-protective potential of SASC is found to be comparable to adipose derived stem cells (ADSCs), with a more potent short term effect. Further, the regenerative potential of two injections of SASC was observed in a rat osteoarthritis model, with SASC attenuating matrix degeneration similar to ADSC treatment. The resulting cartilage in the SASC treated group was also found to be biomechanically competent and similar to ADSC treated cartilage. A second treatment injection was observed to increase joint swelling, i.e. local inflammation. Therefore, a further study was done to evaluate the feasibility of a single SASC injection and identified a higher dose needed to achieve similar histological outcomes compared to the two injection system. Finally, the impact of SASC treatment on immune and inflammatory response in the joint space is studies and in vitro studies are done to show how SASC modulates the major inflammatory pathway involved in osteoarthritis: the NF- κβ pathway. By taking a specific approach to engineer disease modification, SASC compositions can be tailored for other tissues and the system and be expanded to create a tailored stem cell substitute.

Zoom link: https://zoom.us/j/91925139973?pwd=UXhBVDdSVlorSHV1VGtKVDJBUnVIZz09

We invite you to visit Spring Valley Student Farm during the summer! Tours are open to all. The students living and working at SVSF will lead guided tours of the fields, greenhouses, and edible forest garden where we cultivate a wide variety of sustainably grown vegetables, herbs, edible flowers, and small fruits. You will also have the opportunity to learn about our ongoing projects and sustainability initiatives and stay to volunteer if you desire.

Please email the farm manager at Jessica.larkin-wells@uconn.edu or call 203-215-9345 so that we can expect you.

The ID Intercity Grand Rounds are held every Tuesday afternoon
Time: 4:30 – 5:30 PM

Zoom Conference Link: ID Intercity Grand Rounds
Meeting ID: 994 3035 0214
Passcode: 940559

Learning Objectives: Participants will (be able to):

1. Recite the evidence or expert opinion associated with the most critical aspect of the case presented or journal article discussed.
2. Identify one or more barriers to implementing the evidence or expert opinion in practice.
3. Describe one or more strategies necessary either to implement the evidence/expert opinion or overcome any barrier to implementation.

Accreditation: The University of Connecticut School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The University of Connecticut School of Medicine designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Conflict of Interest Policy: All faculty members participating in CME activities provided by the University of Connecticut School of Medicine are required to disclose to the program audience any actual or apparent conflict of interest related to the content of their presentations. Program planners have an obligation to resolve any actual conflicts of interest and share with the audience any safeguards put in place to prevent commercial bias from influencing the content.