Max Liu Lee

All Publications

• Timely Treatment and No Change in Thyroid Cancer Mortality During COVID-19 Pandemic. Reply to Nocini et al. No Impact of COVID-19 Pandemic on Early Mortality for Thyroid Cancer in the US. Comment on "Lee et al. Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery. Curr. Oncol. 2024, 31, 3579-3590". Current oncology (Toronto, Ont.) Lee, M. L., Chen, M. M. 2024; 31 (10): 6270-6271

  Abstract

  We thank Nocini et al [...].

  View details for DOI 10.3390/curroncol31100467

  View details for PubMedID 39451771

• The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration. Bone & joint research Murayama, M., Chow, S. K., Lee, M. L., Young, B., Ergul, Y. S., Shinohara, I., Susuki, Y., Toya, M., Gao, Q., Goodman, S. B. 2024; 13 (9): 462-473

  Abstract

  Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes - the main cellular components in BMAC - interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

  View details for DOI 10.1302/2046-3758.139.BJR-2024-0122.R1

  View details for PubMedID 39237112

• T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells. Journal of biomedical materials research. Part A Murayama, M., Shinohara, I., Toya, M., Susuki, Y., Lee, M. L., Young, B., Gao, Q., Chow, S. K., Goodman, S. B. 2024

  Abstract

  Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.

  View details for DOI 10.1002/jbm.a.37771

  View details for PubMedID 38963690

• Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery. Current oncology (Toronto, Ont.) Lee, M. L., Megwalu, U. C., Finegersh, A., Noel, J. E., Chen, M. M. 2024; 31 (6): 3579-3590

  Abstract

  The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.

  View details for DOI 10.3390/curroncol31060263

  View details for PubMedID 38920746

• Correction: Pius et al. Effects of Aging on Osteosynthesis at Bone-Implant Interfaces. Biomolecules 2024, 14, 52. Biomolecules Pius, A. K., Toya, M., Gao, Q., Lee, M. L., Ergul, Y. S., Chow, S. K., Goodman, S. B. 2024; 14 (3)

  Abstract

  Max L. Lee was not included as an author in the original publication [...].

  View details for DOI 10.3390/biom14030340

  View details for PubMedID 38540803

• Telehealth Usage in Otolaryngology: A Comparative Study Pre- and Post-COVID-19. OTO open Lee, M. L., Wei, E. X., Kandathil, C., Most, S. P. 2024; 8 (1): e109

  Abstract

  The COVID-19 pandemic led to increased telehealth utilization in outpatient otolaryngology settings. While other studies on telehealth usage in otolaryngology settings have focused on demographic disparities during the pandemic, none have yet assessed how these demographic disparities have evolved from before versus after the pandemic. This study examines 4 recent consecutive years of demographic and clinical data from a large hospital system to investigate how the COVID-19 pandemic has changed demographic patterns in telehealth utilization. We demonstrate substantial increases in the number of otolaryngology patients participating in telehealth since the beginning of the COVID-19 pandemic but with no differences in patient distributions by race or ethnicity over time. We also found that telehealth patients, on average, were younger, more likely to be English-speaking, and more likely to be female. While these disparities widened slightly after the start of the pandemic, they were also present prior to the pandemic.

  View details for DOI 10.1002/oto2.109

  View details for PubMedID 38282795

• Effects of Aging on Osteosynthesis at Bone-Implant Interfaces. Biomolecules Pius, A. K., Toya, M., Gao, Q., Ergul, Y. S., Chow, S. K., Goodman, S. B. 2023; 14 (1)

  Abstract

  Joint replacement is a common surgery and is predominantly utilized for treatment of osteoarthritis in the aging population. The longevity of many of these implants depends on bony ingrowth. Here, we provide an overview of current techniques in osteogenesis (inducing bone growth onto an implant), which is affected by aging and inflammation. In this review we cover the biologic underpinnings of these processes as well as the clinical applications. Overall, aging has a significant effect at the cellular and macroscopic level that impacts osteosynthesis at bone-metal interfaces after joint arthroplasty; potential solutions include targeting prolonged inflammation, preventing microbial adhesion, and enhancing osteoinductive and osteoconductive properties.

  View details for DOI 10.3390/biom14010052

  View details for PubMedID 38254652

• C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration. Biomolecules Shinohara, I., Tsubosaka, M., Toya, M., Lee, M. L., Kushioka, J., Murayama, M., Gao, Q., Li, X., Zhang, N., Chow, S. K., Matsumoto, T., Kuroda, R., Goodman, S. B. 2023; 13 (11)

  Abstract

  Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.

  View details for DOI 10.3390/biom13111665

  View details for PubMedID 38002347

• Differences in Noradrenaline Receptor Expression Across Different Neuronal Subtypes in Macaque Frontal Eye Field. Frontiers in neuroanatomy Lee, M., Mueller, A., Moore, T. 2020; 14: 574130

  Abstract

  Cognitive functions such as attention and working memory are modulated by noradrenaline receptors in the prefrontal cortex (PFC). The frontal eye field (FEF) has been shown to play an important role in visual spatial attention. However, little is known about the underlying circuitry. The aim of this study was to characterize the expression of noradrenaline receptors on different pyramidal neuron and inhibitory interneuron subtypes in macaque FEF. Using immunofluorescence, we found broad expression of noradrenaline receptors across all layers of the FEF. Differences in the expression of different noradrenaline receptors were observed across different inhibitory interneuron subtypes. No significant differences were observed in the expression of noradrenaline receptors across different pyramidal neuron subtypes. However, we found that putative long-range projecting pyramidal neurons expressed all noradrenaline receptor subtypes at a much higher proportion than any of the other neuronal subtypes. Nearly all long-range projecting pyramidal neurons expressed all types of noradrenaline receptor, suggesting that there is no receptor-specific machinery acting on these long-range projecting pyramidal neurons. This pattern of expression among long-range projecting pyramidal neurons suggests a mechanism by which noradrenergic modulation of FEF activity influences attention and working memory.

  View details for DOI 10.3389/fnana.2020.574130

  View details for PubMedID 33328901