To assess the safety and efficacy of a novel bladder injection therapy using regenerative medicine in women with refractory interstitial cystitis/bladder pain syndrome (IC/BPS).

This prospective observational study was conducted between January 2019 and December 2023. Women with documented cystoscopic IC/BPS refractory to conventional therapy were enrolled consecutively for the study. An autologous emulsified fat (Nanofat) plus platelet-rich plasma (PRP) combination was prepared intraoperatively. A lesion-targeted injection was performed after cystoscopic hydrodistension of the bladder. Outcomes included pain-VAS, Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), a three-day voiding diary, cystoscopic findings and a scaled global response assessment. Patients who completed a standard protocol of four consecutive treatments at 3-month intervals were followed up every six months post-treatment.

Sixteen (60%) of the 27 patients enrolled completed the treatment course and follow-up visits. Before treatment, 14 (87.5%) patients were found to have cystoscopic abnormalities and were diagnosed with IC. Four patients exhibited Hunner’s ulcers, and ten patients had induced mucosal fissures, denudation and/or petechiae after hydrodistention. The remaining two patients were found to have unremarkable cystoscopic findings and were diagnosed with BPS. The treatment refractory period was an average of 40.7 months, and prior failed treatments included hyaluronic acid instillation, botulinum toxin-A injections and electrofulguration of Hunner’s ulcers. After treatment, all patients reported marked (+3; +3~-3) improvement of their overall bladder conditions at the 6-month and latest follow-up visits (Mean follow-up time: 3 years). Pain-VAS score, ICSI and ISPI scores all improved significantly (p<0.01) post-treatment (Table 1). There was a progressive normalization of bladder mucosal morphology and a remission in various bladder musical lesions (eg. glomerulations, disruptions, and fissures) throughout treatment and this effect was able to be sustained at follow-up (Figure 1). There were no significant adverse events except for transient subcutaneous ecchymosis due to liposuction. The cultured mesenchymal stem cells and purified cytokines/growth factors from nanofat and PRP samples were verified in vitro.

Few clinical trials have used regenerative medicine to treat IC/BPS. Previous studies have assessed the impacts of autologous stromal vascular fraction (SVF) injections and PRP injections on patients with IC/BPS and found the treatments to be safe and effective [1, 2]. However, no studies have reported treatment efficacy with regenerative medicine on bladder morphological results. The normalization of the bladder mucosal morphology with consecutive treatments in this study indicated a tissue repair and regenerative therapeutic effect of the PRP and nanofat combination therapy. This therapy might contribute to an in vivo tissue-engineering process since the grafts contained fundamental elements (eg. stem cells, growth factors, and extracellular matrix) that were required for the process. To ensure adequate mesenchymal stem cell (MSC) yield, laboratory analysis of nanofat samples was conducted, which showed a high SVF and MSC yield. Previous studies have found that combined nanofat and PRP grafting worked better due to a bio-cellular synergistic effect [3]. Therefore, PRP sample analysis was also conducted, which showed a high concentration of growth factors. This further highlighted the synergistic effect of nanofat and PRP, wherein PRP had a high concentration of growth factors, which allowed for tissue repair, whereas nanofat had high SVF and MSC yields, which allowed for long-term tissue regeneration.

Our results suggest that the novel bladder injection therapy using a bio-cellular regenerative medicine provides immediate and sustained safety and efficacy in the treatment of refractory IC/BPS. Surgical efficacy might be attributed to an in vivo tissue engineering process.

Lander EB, Berman MH, See JR. Personal cell therapy for interstitial cystitis with autologous stromal vascular fraction stem cells. Ther Adv Urol. 2019 Aug 17;11:1756287219868590.
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