Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Department of Colorectal Surgery and Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA; Summa Cardiovascular Institute and Northeast Ohio Medical University, Akron, Ohio, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA
Stem Cells Transl Med. 2014 Jun;3(6):760-7. doi: 10.5966/sctm.2013-0157. Epub 2014 May 5.
This research demonstrates the regenerative effects of mesenchymal stem cells (MSCs) on the injured anal sphincter by comparing anal sphincter pressures following intramuscular and serial intravascular MSC infusion in a rat model of anal sphincter injury. Fifty rats were divided into injury (n = 35) and no injury (NI; n = 15) groups. Each group was further divided into i.m., serial i.v., or no-treatment (n = 5) groups and followed for 5 weeks. The injury consisted of an excision of 25% of the anal sphincter complex. Twenty-four hours after injury, 5 × 10(5) green fluorescent protein-labeled MSCs in 0.2 ml of phosphate-buffered saline (PBS) or PBS alone (sham) were injected into the anal sphincter for i.m. treatment; i.v. and sham i.v. treatments were delivered daily for 6 consecutive days via the tail vein. Anal pressures were recorded before injury and 10 days and 5 weeks after treatment. Ten days after i.m. MSC treatment, resting and peak pressures were significantly increased compared with those in sham i.m. treatment (p < .001). When compared with the NI group, the injury groups had anal pressures that were not significantly different 5 weeks after i.m./i.v. treatment. Both resting and peak pressures were also significantly increased after i.m./i.v. MSC treatment compared with treatment with PBS (p < .001), suggesting recovery. Statistical analysis was done using paired t test with Bonferroni correction. Marked decrease in fibrosis and scar tissue was seen in both MSC-treated groups. Both i.m. and i.v. MSC treatment after injury caused an increase in anal pressures sustained at 5 weeks, although fewer cells were injected i.m. The MSC-treated groups showed less scarring than the PBS-treated groups, with the i.v. infusion group showing the least scarring.
这项研究通过比较肌内和连续静脉内间充质干细胞（MSC）输注后肛门括约肌压力，展示了 MSC 对损伤的肛门括约肌的再生作用。将 50 只大鼠分为损伤（n = 35）和未损伤（NI；n = 15）组。每组进一步分为肌内、连续静脉内或无治疗（n = 5）组，并随访 5 周。损伤包括切除 25%的肛门括约肌复合体。损伤后 24 小时，在 0.2 ml 磷酸盐缓冲盐水（PBS）或 PBS 中（假）注射 5 × 10（5）个绿色荧光蛋白标记的 MSC，用于肌内治疗；连续静脉内和假静脉内治疗通过尾巴静脉每天连续 6 天给予。在治疗前、治疗后 10 天和 5 周记录肛门压力。肌内 MSC 治疗后 10 天，静息和峰值压力与假肌内治疗相比显著增加（p <.001）。与 NI 组相比，肌内/静脉内治疗后 5 周时损伤组的肛门压力无显著差异。与 PBS 治疗相比，肌内/静脉内 MSC 治疗后静息和峰值压力也显著增加（p <.001），提示恢复。统计分析采用配对 t 检验，Bonferroni 校正。在 MSC 治疗组中均可见纤维化和疤痕组织明显减少。损伤后肌内和静脉内 MSC 治疗均导致 5 周时肛门压力升高，尽管肌内注射的细胞较少。与 PBS 治疗组相比，MSC 治疗组的疤痕形成较少，静脉内输注组的疤痕形成最少。
