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)

Stanford Advisors


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. n., Lin, T. n., Nabeshima, A. n., Sato, T. n., Gibon, E. n., Jämsen, E. n., Khan, T. N., Yao, Z. n., 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 μCT. 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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