Preclinical investigation of expanded human adipose–derived stem cell dosage and timing for improved defecation function in immunodeficient mice

Abstract: Background Among treatment options for fecal incontinence, none are curative. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents, but most preclinical studies of their effectiveness for anal function have used autologous or allogeneic ADSCs. Here, we investigated the effectiveness, timing of administration, and required dosage of human (h)ADSCs for clinical application. Methods A 10-mm balloon catheter was used to induce anal sphincter injury in immunodeficient mice in three groups: ADSC (hADSCs injected after injury), phosphate-buffered saline (PBS; injected after injury), and control (uninjured). The effects of different timing and number of hADSCs administered was compared among groups using defecation status and pathological evaluation. Results In terms of defecation status, groups receiving ≥ 1 × 10⁴ hADSCs immediately after injection showed improvement. Pathological images showed that compared with the PBS group, the thinnest part of the sphincter was thicker for animals that received ≥ 1 × 10⁴ hADSCs, and fibrosis of the sphincter was notable in those treated with 1 × 10³ hADSCs or PBS. Furthermore, although administration of hADSCs at 30 days following injury yielded no pathological signs of improvement, defecation status was improved. Conclusions hADSC administration in a mouse model of anal sphincter injury was effective. Injection of ≥ 1 × 10⁴ hADSCs was necessary to improve defecation status, an effect detected in both the acute and chronic phases.