P.C. Rossin College of
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Students: Krishna Jayaram

Project: Recapitulating the effects of the osteoarthritis inflammatory environment on mesenchymal stem cell chondrogenesis | View Poster (PDF)

Major: Bioengineering

Advisor: Tomas Gonzalez-Fernandez

Abstract

Osteoarthritis (OA) is a degenerative disease that involves damage to articular cartilage in various joints of the body, mostly the knee, affecting over 240 million people worldwide1. OA has several risk factors that contribute to its degeneration like age, sex, obesity; however, the most predominant risk is the degeneration of osteochondral extracellular matrix within articular joints, leading to inflammation1. Inflammation can be modulated by synovial macrophages such as pro-inflammatory (M1 macrophages) or anti-inflammatory (M2 macrophages). M1 macrophages are recruited to perform pro-inflammatory functions, and release the molecules to induce joint inflammation2. In the initial stages of OA, the secretion of inflammatory cytokines shifts the body to a state of deterioration which is what exacerbates tissue degradation and matrix breakdown3. Mesenchymal stromal cells (MSCs) can be used as a regenerative medicine application due to their ability to differentiate into different cells and to regenerate damaged tissues. Interestingly, utilizing the conditioned media from M1 macrophages (the secretome within the culture media) provides a physiologically relevant means to induce OA onto MSCs, however the ability to regenerate is hampered by inflammation4. The objective of this study is to explore how inflammation affects MSC chondrogenesis by incorporating cell pellets in macrophage conditioned media (MCM). After characterization of GAG and collagen with biochemical assays, we found that MCM stalled chondrogenesis. As we investigate ways to model inflammatory conditions, MCM shows promise to recapitulate the inflammatory environment in OA. Future work will focus on optimizing inflammatory conditions to induce cartilage deterioration.

References:

  1. Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021 Feb 9;325(6):568-578. doi: 10.1001/jama.2020.22171. PMID: 33560326; PMCID: PMC8225295.
  2. Chen Y, Jiang W, Yong H, He M, Yang Y, Deng Z, Li Y. Macrophages in osteoarthritis: pathophysiology and therapeutics. Am J Transl Res. 2020 Jan 15;12(1):261-268. PMID: 32051751; PMCID: PMC7013211.
  3. Kennedy, O., Kitson, A., Okpara, C., Chow, L. W., & Gonzalez-Fernandez, T. (2023). Immunomodulatory strategies for cartilage regeneration in osteoarthritis. Tissue Engineering Part A, doi:10.1089/ten.tea.2023.0255
  4. Spiller, K. L., Wrona, E. A., Romero-Torres, S., Pallotta, I., Graney, P. L., Witherel, C. E., . . . Freytes, D. O. (2016). Differential gene expression in human, murine, and cell line-derived macrophages upon polarization. Experimental Cell Research, 347(1), 1-13. doi:10.1016/j.yexcr.2015.10.017

 

Krishna Jayaram

About Krishna Jayaram

Krishna Jayaram is a sophomore at Lehigh University, majoring in bioengineering (biomaterials and biomechanics track) and minoring in psychology. As a Clare Boothe Luce (CBL) research scholar through the P.C. Rossin College of Engineering and Applied Science, she has been doing research under the guidance of Dr. Tomas Gonzalez-Fernandez. Krishna’s research focuses on developing an  in vitro inflammatory model to mimic osteoarthritis to recapitulate the cellular mechanisms that occur natively and to use this platform as a basis for future anti-inflammatory therapies. Currently, she is working on an inflammation study that utilizes the conditioned media from macrophages in order to investigate the effects of inflammatory cytokines on chondrocyte-derived mesenchymal stromal cells. Following this research, she hopes to pursue a career in prosthetics after graduation. Outside of academia, Krishna enjoys her time as a Gryphon and is the secretary of Leela Indian Fusion dance team.