Adipose-derived mesenchymal stromal cells: A study on safety and efficacy in ocular inflammation

• Published in: The ocular surface 2024-10, Vol.34, p.523-534
• Main Authors: Rusch, Robert M., Inagaki, Emi, Taniguchi, Hiroko, Sakakura, Saki, Tamai, Rie, Nonaka, Hidenori, Shimizu, Shota, Sato, Shinri, Ogawa, Yoko, Masatoshi, Hirayama, Negishi, Kazuno, Okano, Hideyuki, Shimmura, Shigeto
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Adipose-derived stromal cells; Animals; Cells, Cultured; Conjunctiva - pathology; Disease Models, Animal; Female; Graft vs Host Disease - therapy; Graft-versus-host disease (GVHD); Humans; Immunomodulation; Inflammation; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells (MSCs); Mesenchymal Stem Cells - cytology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL
• ISSN: 1542-0124; 1937-5913; 1937-5913
• DOI: 10.1016/j.jtos.2024.11.001

This study explores the application of adipose-derived mesenchymal stromal cells (adMSCs) as a therapy for ocular inflammatory diseases utilizing a chronic GVHD model. Human adMSCs were administered via subconjunctival injection into mice with chronic ocular GVHD. Clinical scores and changes in T cell populations were analyzed. The study showed significant improvement in corneal integrity, including epithelial damage, opacity, thickness, and structure, after subconjunctival adMSC transplantation. Additionally, adMSC transplantation increased CD45+ and Foxp3+ Tregs while decreasing CD4+ T cells, 1IL17A+ Th17 cells, and IFNγ+ Th1 cells in local cervical lymph nodes. Moreover, adMSC-conditioned media enhanced wound closure and cell migration toward the wound bed in vitro. The cells disappeared within a week suggesting that trophic factors were involved. The dual benefit of adMSCs in immune-related ocular disorders underscores their potential for clinical application. This study focuses on subconjunctival delivery, effects of adMSCs and migration post-injection, with implications for optimizing cellular therapy application. The observed dual action, combining immunomodulation and tissue repair enhancement, underscores holistic approach of adMSC therapy in regenerative medicine, making it a potent treatment for diseases involving inflammation and tissue damage in the ocular surface. [Display omitted]