Jonathon Schofield

MSTP in PhD Training

Program: Neurosciences

Current advisor: Matthew D. Wood, PhD

Undergraduate university: University of North Carolina-Chapel Hill, 2016

Enrollment year: 2020

Research summary
Impact of inflammatory milieu on MSC-mediated macrophage polarization.

This past summer, on account of COVID-19-related travel restrictions, I worked remotely from home on an M.Phil in Medical Science (Surgery) degree that I began at the University of Cambridge in the McCaskie Lab under the supervision of Dr. Mark Birch. One of the McCaskie Lab’s primary aims is understanding the complex interactions between mesenchymal stromal cells (MSCs) and innate immune cells to design effective therapies for osteoarthritis (OA), a degenerative joint disease for which there is currently no cure. The innate immune system’s involvement in perpetuating dysregulated inflammatory cascades and tissue destruction that collectively contribute to OA makes its modulation an attractive intervention strategy. Moreover, the well-established observations that MSCs can modify innate immune cells’ phenotype and behavior suggest therapeutic potential. Less well-understood is how an inflammatory milieu impacts the immunomodulatory activity of MSCs, whether endogenous or ex-vivo expanded and administered. Therefore, we designed my project to analyze the effects of distinct combinations and concentrations of inflammatory mediators present in the osteoarthritic joint on MSC immunomodulatory activity. Untreated- and treated-MSC-mediated polarization of proinflammatory M1 macrophages to an anti-inflammatory, pro-reparative M2 phenotype was used as a functional readout and assessed by flow cytometry. Gene transcription, differentiation capacity, and extracellular vesicle contents were additionally evaluated to determine potential mechanisms for enhanced, reduced, or unchanged MSC-mediated M1 to M2 macrophage polarization. Results are intended to 1) inform the selection of adjuncts for MSC-based therapies that promote desirable cellular activity in a challenging microenvironment and 2) guide the design of a robust priming regimen that enhances ex-vivo expanded MSC-guided repair in the context of OA.

Graduate publications