Bio

Boards, Advisory Committees, Professional Organizations

  • Trainee Member, American Epilepsy Society (AES) (2020 - Present)
  • Member, American Veterinary Medical Association (AVMA) (2019 - Present)
  • Associate Member, Orthopedic Research Society (ORS) - Preclinical Models Section (2019 - 2020)
  • Member, Student American Veterinary Medical Association (SAVMA) (2015 - 2019)

Professional Education

  • DVM, Western University of Health Sciences, Veterinary Medicine (2019)
  • PSM, Thomas Jefferson University, Microbiology (2013)

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Publications

All Publications

  • Interleukin-4 repairs wear particle induced osteolysis by modulating macrophage polarization and bone turnover. Journal of biomedical materials research. Part A Pajarinen, J., Lin, T., Nabeshima, A., Sato, T., Gibon, E., Jämsen, E., Khan, T. N., Yao, Z., Goodman, S. B. 2020

    Abstract

    Periprosthetic osteolysis remains as a major complication of total joint replacement surgery. Modulation of macrophage polarization with interleukin-4 (IL-4) has emerged as an effective means to limit wear particle-induced osteolysis. The aim of this study was to evaluate the efficacy of local IL-4 delivery in treating preexisting particle-induced osteolysis. To this end, recently established 8 week modification of murine continuous femoral intramedullary particle infusion model was utilized. Subcutaneous infusion pumps were used to deliver polyethylene (PE) particles into mouse distal femur for 4?weeks to induce osteolysis. IL-4 was then added to the particle infusion for another 4?weeks. This delayed IL-4 treatment (IL-4 Del) was compared to IL-4 delivered continuously (IL-4 Cont) with PE particles from the beginning and to the infusion of particles alone for 8?weeks. Both IL-4 treatments were highly effective in preventing and repairing preexisting particle-induced bone loss as assessed by ?CT. Immunofluorescence indicated a significant reduction in the number of F4/80?+?iNOS?+?M1 macrophages and increase in the number of F4/80?+?CD206?+?M2 macrophages with both IL-4 treatments. Reduction in the number of tartrate resistant acid phosphatase + osteoclasts and increase in the amount of alkaline phosphatase (ALP) + osteoblasts was also observed with both IL-4 treatments likely explaining the regeneration of bone in these samples. Interesting, slightly more bone formation and ALP + osteoblasts were seen in the IL-4 Del group than in the IL-4 Cont group although these differences were not statistically significant. The study is a proof of principle that osteolytic lesions can be repaired via modulation of macrophage polarization.

    View details for DOI 10.1002/jbm.a.37142

    View details for PubMedID 33340244

  • Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur. Cytotherapy Lin, T., Pajarinen, J., Kohno, Y., Maruyama, M., Romero-Lopez, M., Huang, J., Nathan, K., Khan, T. N., Yao, Z., Goodman, S. B. 2018

    Abstract

    BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation.METHODS: Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFkappaB) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model.RESULTS: The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5?*?106) and low (0.5?*?106) cell-injected groups. Injection of 2.5?*?106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5?*?106 constitutive IL-4 or NFkappaB-sensing IL-4-secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NFkappaB-sensing IL-4-secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)alpha and IL-1beta secretion were observed between the MSC-transplanted and control groups in the explant culture.DISCUSSION: Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4-secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation.

    View details for PubMedID 30077567

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