The therapeutic effects of primed fresh OCT4-enriched mesenchymal stem cells in a mouse model of radiation cystitis

<title>Abstract</title> <p>Introduction : There is no curative therapy for radiation cystitis (RC), an unpredictable complication of treating pelvic organ malignancies with radiation therapy (RT). A mouse model of RC was developed to evaluate the efficacy of primed fresh OCT4 (PFO)-enriched mesenchymal stem cells (PFO-MSCs). Methods Five mice (six-week-old female C57BL/6) from the sham, 20 Gy, and 30 Gy groups (n = 15/group) were sacrificed on weeks 4, 8, and 12 after radiation for histological bladder examination. To evaluate the efficacy of PFO-MSCs, mice were divided into the sham, RC, and RC + PFO groups (n = 5/group). Voiding spot assays were used to assess voiding profiles, and bladders were harvested one-week post-injection. Separate mouse cohorts (n = 5/group in each assay) were used for histology and transcriptomic analyses because of the mouse bladder’s limited tissue. Weekly voiding spot assays (up to four weeks) were performed to assess long-term efficacy after stem cell injection in the RC + PFO group. Results The optimal radiation dose for RC was 20Gy, and urination was more frequent in irradiated mice and more evident eight weeks post-RT. The RC group’s bladder tissue had edema and ischemic necrosis of the urothelium with increased detrusor inflammation and fibrosis. PFO-MSCs alleviated histological changes and improved urinary frequency, with their efficacy lasting up to eight weeks. Transcriptomic analysis revealed that PFO-MSCs partially reversed radiation-induced transcriptional alterations and restored tissue homeostasis-, cell adhesion-, metabolism-, and muscle-related biological processes-associated gene programs. Conclusion PFO-MSCs improved urinary frequency and alleviated ischemic urothelial necrosis, inflammation, and bladder fibrosis.</p>