A research team led by Professors Minyong Kang and Kwangjin Ko of the Department of Urology at Samsung Medical Center announced that they have identified a new pathogenic mechanism underlying interstitial cystitis (bladder pain syndrome), an intractable disease whose clear cause had remained unknown, by employing state-of-the-art bio-technologies. The study was published in the latest issue of Experimental & Molecular Medicine (EMM, IF=17.5), a world-renowned journal in the field of translational medicine, drawing significant attention from the academic community.
Interstitial cystitis is a representative intractable disease characterized by damage to the bladder lining and chronic inflammation, resulting in severe pelvic pain, urinary frequency, and urgency. Because the precise cause of the disease had remained unclear, fundamental treatment had not been possible, and the wide variation in symptoms among patients has posed considerable challenges to treatment. Previously, the disease had been classified based simply on visual (endoscopic) findings, an approach with clear limitations in explaining the specific cellular-level causes underlying disease onset.
To address this, the research team obtained full-thickness bladder tissue from patients. This represented a substantial departure from previous studies, which had been limited to techniques based on superficial mucosal biopsy samples obtained via cystoscopy, examining only simple changes in cell distribution or differences in gene expression. The research team reported that securing and analyzing both the patients' ulcerative lesions (Hunner lesions) and the non-lesion areas serving as controls—both as full-thickness bladder tissue—was key to ensuring the study's high clinical value and reliability.
The team also applied single-cell transcriptomic technology, which analyzes the genes of individual cells, together with high-resolution spatial transcriptomic technology, which precisely captures the positional information of cells. Through this combined approach, the researchers successfully identified a "multicellular network" of complex signaling interactions among stromal cells, immune cells, and vascular cells within the bladder tissue that drive the disease, the team explained.
Notably, rather than outsourcing sample analysis to external institutions, the team used the single-cell sequencing and high-resolution spatial transcriptomic (Visium HD) infrastructure of Samsung Medical Center's Translational Genomics Center, enabling the rapid and consistent production of highly reliable genomic data.
The research team confirmed that specific inflammation-inducing immune cells (Th17 cells and M2 macrophages) become activated in diseased areas, driving abnormal vascular changes. They also found that a specific signaling pathway between vascular cells and muscle cells becomes abnormally intensified, leading to severe remodeling and excessive contraction of the bladder muscle.
This study also solved the mystery of why patients with interstitial cystitis experience severe chronic pain despite having no discernible abnormality in the nervous system. The team demonstrated that a specific cluster of neuron-like fibroblasts within the bladder markedly activates a pain-amplifying signaling pathway, continuously exchanging signals with muscle cells to generate pain.
Professor Kwangjin Ko stated, "This study is significant in that it systematically analyzed, at the cellular level, a disease that had previously been diagnosed only through visual findings, and directly demonstrated in patient tissue that organic networks among cells are a key cause of the disease. It is expected to serve as an important cornerstone for identifying new therapeutic targets going forward."
Professor Minyong Kang emphasized, "By combining cutting-edge genomic technologies, we have mapped out the microenvironment within the bladder of patients with interstitial cystitis like a detailed chart. Having identified the specific cells and signaling pathways responsible for bladder overcontraction and pelvic pain, we expect this will lead to the development of fundamental, cause-targeted treatments for patients with intractable interstitial cystitis."
This research was supported by national research funding from the Ministry of Science and ICT, the National Research Foundation of Korea, the Ministry of Health and Welfare, the Korea Health Industry Development Institute, and the Ministry of Trade, Industry and Energy.