de la Portilla Fernando, Yuste Yaiza, Pereira Sheila, Olano Carolina, Maestre Maria Victoria, Padillo Francisco Javier
Department of General and Digestive Surgery, Unit Colorectal Surgery, "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville, Seville, Spain.
Institute of Biomedicine of Seville (IBiS), "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville, Seville, Spain.
Int J Stem Cells. 2018 May 30;11(1):39-47. doi: 10.15283/ijsc17074.
Multipotent mesenchymal stem cells (MSCs) have been used in inflammatory bowel diseases because of their immunomodulatory and regenerative properties. We investigated their local use in an experimental model of colitis in the rat.
Colitis was induced into 20 Wistar rats with local TNBS instillation. Allogeneic stem cells were derived from rat adipose tissue and labeled with PKH2 linker dye with creation of a control and a second group treated by a local injection into the rectal wall of 2×10⁶ allogeneic adipose tissue-derived stem cells (ADSCs). The thicknesses of different components of the rectum were measured with comparisons made in different parts of the colon of the Hunter inflammatory score. PKH2-dyed ADSCs were detected by fluorescence microscopy.
Total colitis was induced in 19/20 rats with homing of fluorescent ADSCs. to the crypt base and perivascular space of the submucosa. There were no differences in component rectal wall thicknesses with a higher Hunter score in the treated group compared with the controls, in the rectum (3.8±2.74 vs. 1.5±2.37, respectively; p=0.017) and in right colon (2.5±1.08 vs. 0.20±0.42, respectively; p=0.0001). Local colonic injection of allogeneic adipose stem cells. in experimental colitis is feasible and safe. There is demonstrable homing of cells in chemically-induced colitis both to the treated region and parts of the colon distant to the MSC treatment site. Such cells readily proliferate and could potentially be a source for future treatment of resistant disease.
多能间充质干细胞（MSCs）因其免疫调节和再生特性已被用于炎性肠病。我们在大鼠结肠炎实验模型中研究了它们的局部应用。
通过局部滴注TNBS诱导20只Wistar大鼠患结肠炎。同种异体干细胞来源于大鼠脂肪组织，用PKH2连接染料标记，分为对照组和第二组，第二组通过向直肠壁局部注射2×10⁶个同种异体脂肪组织来源的干细胞（ADSCs）进行治疗。用Hunter炎症评分法比较结肠不同部位的直肠各组成部分厚度。通过荧光显微镜检测PKH2染色的ADSCs。
19/20只大鼠诱发了全结肠炎，荧光ADSCs归巢至隐窝底部和黏膜下层的血管周围间隙。与对照组相比，治疗组直肠壁各组成部分厚度无差异，但直肠（分别为3.8±2.74和1.5±2.37；p=0.017）和右结肠（分别为2.5±1.08和0.20±0.42；p=0.0001）的Hunter评分更高。在实验性结肠炎中局部注射同种异体脂肪干细胞是可行且安全的。在化学诱导的结肠炎中，可证明细胞归巢至治疗区域以及距MSC治疗部位较远的结肠部分。此类细胞易于增殖，可能成为未来治疗难治性疾病的来源。
