Immunomodulatory potential of human dermal fibroblast spheroids in psoriasis therapy

Summary: Abstract Body: Psoriasis is a chronic, immune-mediated skin disease with limited options for achieving sustained remission. This study investigates the therapeutic potential of human dermal fibroblast (HDF) spheroids as a cell-based therapy. HDFs were cultured into three-dimensional spheroids (1x106 cells/mouse, 1,733 cells in each spheroid with an average diameter of 150 mm) and assessed in mouse models of imiquimod (IMQ)-induced psoriasis. A single dose of HDF spheroids significantly reduced skin lesion severity in mild psoriasis, normalized blood cell counts, alleviated spleen enlargement, and improved cytokine dysregulation. In moderate-to-severe cases, repeated doses were required to achieve similar efficacy. Moreover, HDF spheroids demonstrated therapeutic efficacy comparable to multiple doses of an anti-IL-23 monoclonal antibody, a standard psoriasis treatment. Importantly, HDF spheroids inhibited monocyte production and infiltration in the spleen and skin—an immunomodulatory mechanism not observed with anti-IL-23 therapy. In the SKH-1 hairless mouse model with a cyclic IMQ regimen mimicking the chronic and relapsing nature of human psoriasis, HDF spheroids administered during the initial disease cycle alleviated severity and reduced relapse likelihood in subsequent cycles. These findings suggest HDF spheroids' immunomodulatory and translational potential as a practical, durable therapy for psoriasis. Their distinct mechanism of action and scalability make them a promising cell-based approach for managing psoriasis and other chronic skin inflammatory diseases. Chuo Fang¹, Inah Embile¹, Christen Boyer¹, Simon Gebremeskel¹, Nikolay Bazhanov¹, Midori Taruishi¹, Phillip Baker¹, Kelsey Howard¹, Pete O. Heeron¹, Hamid Khoja¹ 1. FibroBiologics, Houston, TX, United States. Translational Studies: Preclinical