Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan;
In Vivo. 2024 Mar-Apr;38(2):546-558. doi: 10.21873/invivo.13473.
BACKGROUND/AIM: Although certain treatment options exist for intestinal 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. In this study, the effectiveness, timing of administration, and required dosage of human ADSCs were investigated for clinical application.
A 10-mm balloon catheter was used to induce anal sphincter injury in immunodeficient mice in the following experimental groups (n=4 per group): ADSC (injected ADSCs after injury), PBS (injected phosphate-buffered saline after injury), and control (uninjured). The effects of different timing (immediately after injection and 30 days following injury) and number of human ADSCs administered was compared among groups based on defecation status and pathological evaluation.
In terms of defecation status, groups receiving ≥1×10 human ADSCs after injection showed improvement. Pathological images showed that compared to the PBS group, the thinnest part of the sphincter was thicker for animals that received ≥1×10 human ADSCs, and fibrosis of the sphincter was notable in those treated with 1×10 human ADSCs or PBS. Furthermore, defecation status was improved by administration of human ADSCs, not only immediately after injury, but also at 30 days following injury.
Human ADSC administration in a mouse model of anal sphincter injury was effective. Injection of ≥1×10 human ADSCs was the amount necessary to improve defecation status, an effect detected in both the acute and chronic phases.
背景/目的：尽管存在一些治疗肠失禁的方法，但没有一种是根治性的。脂肪源性干细胞（ADSCs）已成为有前途的治疗剂，但大多数关于其对肛门功能有效性的临床前研究都使用了自体或同种异体 ADSCs。在这项研究中，研究了人 ADSCs 的有效性、给药时间和所需剂量，以用于临床应用。
在以下实验分组中（每组 4 只），使用 10mm 球囊导管诱导免疫缺陷小鼠的肛门括约肌损伤：ADSC（损伤后注射 ADSCs）、PBS（损伤后注射磷酸盐缓冲液）和对照组（未损伤）。根据排便情况和病理评估，比较了不同时间（注射后立即和损伤后 30 天）和给予的人 ADSCs 数量对各组的影响。
在排便状态方面，注射后给予≥1×10 个 ADSC 的组有所改善。病理图像显示，与 PBS 组相比，接受≥1×10 个 ADSC 的动物的括约肌最薄部分较厚，接受 1×10 个 ADSC 或 PBS 治疗的动物的括约肌纤维化明显。此外，人 ADSC 的给药不仅在损伤后立即，而且在损伤后 30 天也改善了排便状态。
在肛门括约肌损伤的小鼠模型中，给予人 ADSC 是有效的。注射≥1×10 个 ADSC 是人 ADSC 改善排便状态的必要数量，在急性和慢性阶段均有效果。
